59 results on '"Ioannis Efstratiou"'
Search Results
2. Mismatch repair deficiency and aberrations in the Notch and Hedgehog pathways are of prognostic value in patients with endometrial cancer.
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Genovefa Polychronidou, Vassiliki Kotoula, Kyriaki Manousou, Ioannis Kostopoulos, Georgia Karayannopoulou, Eleni Vrettou, Mattheos Bobos, Georgia Raptou, Ioannis Efstratiou, Dimitrios Dionysopoulos, Kyriakos Chatzopoulos, Sotirios Lakis, Sofia Chrisafi, Dimitrios Tsolakidis, Alexios Papanikolaou, Nikolaos Dombros, and George Fountzilas
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Medicine ,Science - Abstract
The aim of this study was to investigate the prognostic value of the Hedgehog (Gli, Patched-1, Shh, Smo) and Notch (Jag1, Notch2, Notch3) pathway members, in comparison to a panel of proteins (ER, PgR, HER2/neu, Ki67, p53, p16, PTEN and MMR) previously suggested to be involved in the pathogenesis of endometrial cancer, in association with clinical outcome and standard clinicopathological characteristics. A total of 204 patients with histological diagnosis of endometrial cancer treated from 2004 to 2013 were included. The evaluation of protein expression was assessed by immunohistochemistry. Univariate analysis showed that higher Ki67 labeling, expression of PTEN, p16, Notch2 and Notch3 proteins, as well as MMR proficiency were associated with increased relapse and mortality rate. Additionally, Patched-1 protein expression was associated with worse DFS, while p53 overexpression was associated with worse OS. In multivariate analyses, patients with MMR proficient tumors had more than double risk for death than patients with MMR deficient (MMRd) tumors (adjusted HR = 2.19, 95% CI 1.05-4.58, p = 0.036). Jag1 positivity conferred reduced mortality risk (HR = 0.48, 95% CI 0.23-0.97, p = 0.042). However, as shown by hierarchical clustering, patients fared better when their tumors expressed high Jag1 protein in the absence of Notch2 and Notch3, while they fared worse when all three proteins were highly expressed. Patched-1 positivity conferred higher risk for relapse (HR = 2.04, 95% CI 1.05-3.96, p = 0.036). Aberrant expression of key components of the Notch and Hedgehog signaling pathways, as well as MMRd may serve as independent prognostic factors for recurrence and survival in patients with endometrial cancer.
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- 2018
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3. Intercostal leiomyoma in a child: review of the literature
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Kleanthis Anastasiadis, Chrysostomos Kepertis, Ioannis Efstratiou, Evgenia Babatseva, and Ioannis Spyridakis
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leiomyoma ,intercostal space ,chest wall ,child ,Medicine - Abstract
Leiomyomas of the chest wall are very rare. In a review of the current literature twelve cases were found, of which only one concerns of an intercostal leiomyoma of the chest wall. We report a case of 1 year old male child with intercostal leiomyoma who presented with a painless rigid swelling of the right chest wall. The radiological control revealed a solid mass in the right anterior sixth intercostal space. En-bloc excision of the mass by abrading of the sixth rib through right anterior thoracotomy was performed. Histopatological analysis showed a localized intercostal leiomyoma. The patient has a close follow-up for 6 months without evidence of recurrence. This is the first case of a primary intercostal leiomyoma in a child which was excised totally without reconstruction of the chest wall.
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- 2017
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4. Tumor Infiltrating Lymphocytes Affect the Outcome of Patients with Operable Triple-Negative Breast Cancer in Combination with Mutated Amino Acid Classes.
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Vassiliki Kotoula, Sotiris Lakis, Ioannis S Vlachos, Eleni Giannoulatou, Flora Zagouri, Zoi Alexopoulou, Helen Gogas, Dimitrios Pectasides, Gerasimos Aravantinos, Ioannis Efstratiou, George Pentheroudakis, Kyriaki Papadopoulou, Kyriakos Chatzopoulos, Pavlos Papakostas, Maria Sotiropoulou, Irene Nicolaou, Evangelia Razis, Amanda Psyrri, Paris Kosmidis, Christos Papadimitriou, and George Fountzilas
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Medicine ,Science - Abstract
Stromal tumor infiltrating lymphocytes (TILs) density is an outcome predictor in triple-negative breast cancer (TNBC). Herein we asked whether TILs are related to coding mutation load and to the chemical class of the resulting mutated amino acids, i.e., charged, polar, and hydrophobic mutations.We examined paraffin tumors from TNBC patients who had been treated with adjuvant chemotherapy mostly within clinical trials (training cohort, N = 133; validation, N = 190) for phenotype concordance; TILs density; mutation load and types.Concordance of TNBC phenotypes was 42.1% upon local / central, and 72% upon central / central pathology assessment. TILs were not associated with mutation load, type and class of mutated amino acids. Polar and charged mutation patterns differed between TP53 and PIK3CA (p50% TILs tumors (training p = 0.003; validation p = 0.015).TILs density is unrelated to mutation load in TNBC, which may be regarded as an unstable phenotype. If further validated, hydrophobic mutations along with TILs density may help identifying TNBC patients in higher risk for relapse.
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- 2016
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5. Significance of PIK3CA Mutations in Patients with Early Breast Cancer Treated with Adjuvant Chemotherapy: A Hellenic Cooperative Oncology Group (HeCOG) Study.
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George Papaxoinis, Vassiliki Kotoula, Zoi Alexopoulou, Konstantine T Kalogeras, Flora Zagouri, Eleni Timotheadou, Helen Gogas, George Pentheroudakis, Christos Christodoulou, Angelos Koutras, Dimitrios Bafaloukos, Gerasimos Aravantinos, Pavlos Papakostas, Elpida Charalambous, Kyriaki Papadopoulou, Ioannis Varthalitis, Ioannis Efstratiou, Thomas Zaramboukas, Helen Patsea, Chrisoula D Scopa, Maria Skondra, Paris Kosmidis, Dimitrios Pectasides, and George Fountzilas
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Medicine ,Science - Abstract
The PI3K-AKT pathway is frequently activated in breast cancer. PIK3CA mutations are most frequently found in the helical (exon 9) and kinase (exon 20) domains of this protein. The aim of the present study was to examine the role of different types of PIK3CA mutations in combination with molecular biomarkers related to PI3K-AKT signaling in patients with early breast cancer.Tumor tissue samples from 1008 early breast cancer patients treated with adjuvant chemotherapy in two similar randomized trials of HeCOG were examined. Tumors were subtyped with immunohistochemistry (IHC) and FISH for ER, PgR, Ki67, HER2 and androgen receptor (AR). PIK3CA mutations were analyzed by Sanger sequencing (exon 20) and qPCR (exon 9) (Sanger/qPCR mutations). In 610 cases, next generation sequencing (NGS) PIK3CA mutation data were also available. PIK3CA mutations and PTEN protein expression (IHC) were analyzed in luminal tumors (ER and/or PgR positive), molecular apocrine carcinomas (MAC; ER/PgR negative / AR positive) and hormone receptor (ER/PgR/AR) negative tumors.PIK3CA mutations were detected in 235/1008 tumors (23%) with Sanger/qPCR and in 149/610 tumors (24%) with NGS. Concordance between the two methods was good with a Kappa coefficient of 0.76 (95% CI 0.69-0.82). Lobular histology, low tumor grade and luminal A tumors were associated with helical domain mutations (PIK3CAhel), while luminal B with kinase domain mutations (PIK3CAkin). The overall incidence of PIK3CA mutations was higher in luminal as compared to MAC and hormone receptor negative tumors (p = 0.004). Disease-free and overall survival did not significantly differ with respect to PIK3CA mutation presence and type. However, a statistically significant interaction between PIK3CA mutation status and PTEN low protein expression with regard to prognosis was identified.The present study did not show any prognostic significance of specific PIK3CA mutations in a large group of predominantly lymph-node positive breast cancer women treated with adjuvant chemotherapy. Further analyses in larger cohorts are warranted to investigate possible differential effect of distinct PIK3CA mutations in small subgroups of patients.
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- 2015
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6. Differential expression of the insulin-like growth factor receptor among early breast cancer subtypes.
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Giannis Mountzios, Dimitra Aivazi, Ioannis Kostopoulos, Helen P Kourea, George Kouvatseas, Eleni Timotheadou, Pantelis Zebekakis, Ioannis Efstratiou, Helen Gogas, Chrisanthi Vamvouka, Sofia Chrisafi, Anastasios Stofas, George Pentheroudakis, Angelos Koutras, Eleni Galani, Dimitrios Bafaloukos, and George Fountzilas
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Medicine ,Science - Abstract
INTRODUCTION: We sought to determine the level of protein expression of the critical components of the insulin-like growth factor receptor (IGFR) pathway and to evaluate their prognostic significance across the different early breast cancer subtypes. PATIENTS AND METHODS: Archival tumor tissue from 1,021 women with early, node positive breast cancer, who were prospectively evaluated within two randomized clinical trials, was used to construct tissue microarrays that were stained for hormone receptors (HR), Ki67, HER2, epidermal growth factor receptor (EGFR) and cytokeratins 5/6, to classify tumors into five immunophenotypical subgroups. Immunohistochemical (IHC) expression of IGF1R-alpha and beta subunits, IGF2R and IGF-binding protein 2 (IGFBP2) was assessed using the immunoreactive score (IRS). Repeated internal cross-validation was performed to examine the statistical validity of the cut off points for all biomarkers. RESULTS: After a median follow-up time of 105.4 months, overall 370 women (36.2%) had relapsed and 270 (26.4%) had died. Tumors expressing IGF1R-alpha above the median IRS were significantly more frequently HR positive (luminal A+B+HER2), as compared to HER2-enriched and triple negative ones (p
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- 2014
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7. Adjusting breast cancer patient prognosis with non-HER2-gene patterns on chromosome 17.
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Vassiliki Kotoula, Mattheos Bobos, Zoi Alexopoulou, Christos Papadimitriou, Kyriaki Papadopoulou, Elpida Charalambous, Eleftheria Tsolaki, Grigorios Xepapadakis, Irene Nicolaou, Irene Papaspirou, Gerasimos Aravantinos, Christos Christodoulou, Ioannis Efstratiou, Helen Gogas, and George Fountzilas
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Medicine ,Science - Abstract
BACKGROUND: HER2 and TOP2A gene status are assessed for diagnostic and research purposes in breast cancer with fluorescence in situ hybridization (FISH). However, FISH probes do not target only the annotated gene, while chromosome 17 (chr17) is among the most unstable chromosomes in breast cancer. Here we asked whether the status of specifically targeted genes on chr17 might help in refining prognosis of early high-risk breast cancer patients. METHODS: Copy numbers (CN) for 14 genes on chr17, 4 of which were within and 10 outside the core HER2 amplicon (HER2- and non-HER2-genes, respectively) were assessed with qPCR in 485 paraffin-embedded tumor tissue samples from breast cancer patients treated with adjuvant chemotherapy in the frame of two randomized phase III trials. PRINCIPAL FINDINGS: HER2-genes CN strongly correlated to each other (Spearman's rho >0.6) and were concordant with FISH HER2 status (Kappa 0.6697 for ERBB2 CN). TOP2A CN were not concordant with TOP2A FISH status (Kappa 0.1154). CN hierarchical clustering revealed distinct patterns of gains, losses and complex alterations in HER2- and non-HER2-genes associated with IHC4 breast cancer subtypes. Upon multivariate analysis, non-HER2-gene gains independently predicted for shorter disease-free survival (DFS) and overall survival (OS) in patients with triple-negative cancer, as compared to luminal and HER2-positive tumors (interaction p = 0.007 for DFS and p = 0.011 for OS). Similarly, non-HER2-gene gains were associated with worse prognosis in patients who had undergone breast-conserving surgery as compared to modified radical mastectomy (p = 0.004 for both DFS and OS). Non-HER2-gene losses were unfavorable prognosticators in patients with 1-3 metastatic nodes, as compared to those with 4 or more nodes (p = 0.017 for DFS and p = 0.001 for OS). CONCLUSIONS: TOP2A FISH and qPCR may not identify the same pathology on chr17q. Non-HER2 chr17 CN patterns may further predict outcome in breast cancer patients with known favorable and unfavorable prognosis.
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- 2014
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8. Prognostic significance of ESR1 gene amplification, mRNA/protein expression and functional profiles in high-risk early breast cancer: a translational study of the Hellenic Cooperative Oncology Group (HeCOG).
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George Pentheroudakis, Vassiliki Kotoula, Anastasia G Eleftheraki, Eleftheria Tsolaki, Ralph M Wirtz, Konstantine T Kalogeras, Anna Batistatou, Mattheos Bobos, Meletios A Dimopoulos, Eleni Timotheadou, Helen Gogas, Christos Christodoulou, Kyriaki Papadopoulou, Ioannis Efstratiou, Chrisoula D Scopa, Irene Papaspyrou, Dimitrios Vlachodimitropoulos, Helena Linardou, Epaminontas Samantas, Dimitrios Pectasides, Nicholas Pavlidis, and George Fountzilas
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Medicine ,Science - Abstract
BackgroundDiscrepant data have been published on the incidence and prognostic significance of ESR1 gene amplification in early breast cancer.Patients and methodsFormalin-fixed paraffin-embedded tumor blocks were collected from women with early breast cancer participating in two HeCOG adjuvant trials. Messenger RNA was studied by quantitative PCR, ER protein expression was centrally assessed using immunohistochemistry (IHC) and ESR1 gene copy number by dual fluorescent in situ hybridization probes.ResultsIn a total of 1010 women with resected node-positive early breast adenocarcinoma, the tumoral ESR1/CEP6 gene ratio was suggestive of deletion in 159 (15.7%), gene gain in 551 (54.6%) and amplification in 42 cases (4.2%), with only 30 tumors (3%) harboring five or more ESR1 copies. Gene copy number ratio showed a significant, though weak correlation to mRNA and protein expression (Spearman's Rho ConclusionsESR1 gene deletion and amplification do not constitute per se prognostic markers, instead they can be classified to distinct prognostic groups according to their protein-mediated functional status.
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- 2013
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9. Angiogenic and Antiangiogenic VEGFA Splice Variants in Colorectal Cancer: Prospective Retrospective Cohort Study in Patients Treated With Irinotecan-Based Chemotherapy and Bevacizumab
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Christina Bamia, Epaminontas Samantas, Georgia Kafiri, Dimitrios Bafaloukos, George Fountzilas, Sofia Chrisafi, Ioannis Efstratiou, Dimitrios Pectasides, Kyriaki Papadopoulou, Iliada Bombolaki, George Pentheroudakis, Thomas Makatsoris, Leonidas Mavroeidis, Georgia-Angeliki Koliou, Kyriakos Chatzopoulos, Kalliopi Petraki, Helen P. Kourea, George Papatsibas, Vassiliki Kotoula, Pavlos Papakostas, and Davide Mauri
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Male ,Vascular Endothelial Growth Factor A ,Oncology ,Colorectal cancer ,Leucovorin ,Angiogenesis Inhibitors ,chemistry.chemical_compound ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,Protein Isoforms ,Prospective Studies ,Hazard ratio ,Gastroenterology ,Middle Aged ,Prognosis ,Primary tumor ,Bevacizumab ,Gene Expression Regulation, Neoplastic ,Oxaliplatin ,Survival Rate ,Vascular endothelial growth factor ,030220 oncology & carcinogenesis ,FOLFIRI ,Female ,030211 gastroenterology & hepatology ,Fluorouracil ,Colorectal Neoplasms ,medicine.drug ,medicine.medical_specialty ,Irinotecan ,03 medical and health sciences ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Capecitabine ,Aged ,Retrospective Studies ,business.industry ,medicine.disease ,Alternative Splicing ,chemistry ,Drug Resistance, Neoplasm ,Angiogenesis Inducing Agents ,Camptothecin ,business ,Follow-Up Studies - Abstract
Background Alternative splicing of vascular endothelial growth factor A (VEGFA) results in VEGFAxxxb antiangiogenic isoforms that fail to activate angiogenesis. Bevacizumab, widely used in patients with metastatic colorectal cancer (CRC), binds both VEGFA and VEGFAxxxb isoforms. Patients and Methods Formalin-fixed, paraffin-embedded primary tumors from metastatic CRC patients treated with first-line FOLFIRI (leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin) + bevacizumab (n = 285) or FOLFIRI only (n = 75) were collected. The relative expression of VEGFA121a, 121b, 145a, 145b, 165a, and 165b was assessed with custom TaqMan-MGB assays and quantitative PCR. Results At a median follow-up of 101.5 months, left-sided primary CRC was a favorable prognosticator (median survival, 29.2 vs. 18.2 months; P = .015). Positive high VEGFA145b was an unfavorable factor for progression-free survival (PFS; hazard ratio [HR] = 1.66; 95% confidence interval [CI], 1.13-2.44; P = .009) in patients who received FOLFIRI + bevacizumab, without prognostic significance in FOLFIRI-only patients (HR = 0.70; 95% CI, 0.34-1.44; P = .33). The adverse effect on PFS of 145b was more pronounced in patients with right-sided colon cancer (HR = 2.62; 95% CI, 1.35-5.12; P = .005), especially in those who received bevacizumab (HR = 2.85; 95% CI, 1.31-6.21; P = .008). In patients with right-sided colon primary tumors, isoform 121b correlated with inferior PFS (HR = 1.73; 95% CI, 0.94-3.18; P = .076) and overall survival (OS; HR = 2.0; 95% CI, 1.08-3.72; P = .028). In patients with left-sided primary tumors, positive high 165b correlated with superior PFS (HR = 0.76; 95% CI, 0.59-0.99; P = .044) and OS (HR = 0.68; 95% CI, 0.52-0.90; P = .006). At multivariate analysis, right-sided primary tumor was associated with inferior PFS (HR = 1.28; 95% CI, 1.00-1.64), while 145b consistently retained predictive significance for lack of benefit in PFS with bevacizumab (HR = 1.71; 95% CI, 1.16-2.53). Multivariate analysis for OS showed that VEGFA165b expression was favorable in patients with left-sided but unfavorable in patients with right-sided primary tumors (Pinteraction Conclusion The antiangiogenic isoform VEGFA145b messenger RNA may predict resistance to bevacizumab. Differences in biological relevance and prognostic significance of various VEGFA isoforms were found for right- versus left-sided primary tumors.
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- 2019
10. Abstract P4-08-13: Prognostic significance of CD8+ tumor-infiltrating lymphocytes (TILs) in patients with early breast cancer (EBC) treated with dose-dense sequential adjuvant chemotherapy (dds-CT). An observational study (ACTRN12616001043426)
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A. Psyrri, Alexandra Papoudou-Bai, D.G. Pectasides, Helen Gogas, Georgios Pentheroudakis, Sofia Chrisafi, I. Nicolaou, Maria Sotiropoulou, Gerassimos Aravantinos, C Petraki, C. Christodoulou, Flora Zagouri, Angelos Koutras, Anna Batistatou, G-A Koliou, Triantafyllia Koletsa, G. Fountzilas, Helen P. Kourea, Mattheos Bobos, Petroula Arapantoni-Dadioti, Vasiliki Kotoula, Ioannis Efstratiou, and A. Visvikis
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Oncology ,Cancer Research ,medicine.medical_specialty ,Stromal cell ,Tumor-infiltrating lymphocytes ,business.industry ,medicine.medical_treatment ,Cancer ,medicine.disease ,Radiation therapy ,Breast cancer ,Docetaxel ,Trastuzumab ,Internal medicine ,medicine ,business ,medicine.drug ,Epirubicin - Abstract
Background - aim: Information on the prognostic role of cytotoxic CD8+ T cells in the era of modern adjuvant CT is limited. The primary objective of the present report is to assess the prognostic impact of CD8+ cells in patients with intermediate or high-risk EBC (T1-3N1-2M0) treated with dds-CT. Secondary endpoints are safety, disease-free survival (DFS) and overall survival (OS). Patients and Methods: Patients (N=1,000) were treated with 4 cycles of Epirubicin, 75mg/m2, and Cyclophophamide, 600mg/m2 every 2 weeks followed by 4 cycles of Docetaxel (D), 100mg/m2 every 3 weeks with G-CSF support in all cycles. Trastuzumab was initiated concurrently with D and continued for a total of 1 year. Hormonal and radiation therapy were given post CT, as indicated. Formalin-fixed paraffin-embedded tumors were available for 642 patients (64.2%) and were centrally assessed for immunohistochemical subtypes (IHC4; N=526), stromal TILs density by morphology (N=636), as well as stromal and intratumoral cytotoxic CD8+ T cell numbers (N=554). TILs and CD8+ were assessed as continuous variables for associations and as 10% increments for outcome. Results: In total, 901/1,000 pts (90.1%) completed 8 cycles of CT. Severe (gradeIII-IV) toxicitiesincludedneutropenia (5.6%), leucopenia (3.6%), lymphopenia (2.1%), hand-footsyndrome (2.1%), and hepatotoxicity (1.8%). Febrileneutropenia occurred in 1.6% of the patients. The 5-year DFS and OS rates were 89.5% and 93.1%, respectively. Luminal A tumors were classified in 26.2%, Luminal B in 35.2%, luminal HER2 in 9.5%; HER2-enriched in 7.2%; and, triple-negative (TNBC) in 21.9% of informative patients. Among subtypes, stromal TILs density was higher in HER2-enriched and TNBC (p Conclusions: In this study, dds-CT was well tolerated and active in patients with EBC. We confirm the presence of morphologically assessed higher TILs density, and of higher cytotoxic CD8+ T cell numbers in hormone receptor negative EBC, as well as the favorable prognostic impact of higher stromal TILs density in TNBC. In comparison to stromal TILs density, higher stromal CD8+ may confer favorable prognosis irrespectively of EBC subtype. Stromal CD8+ seems to be a marker worth further standardizing for reporting on immune cell infiltrates in EBC. Citation Format: Kourea HP, Koletsa T, Kotoula V, Koliou G-A, Batistatou A, Pentheroudakis G, Arapantoni-Dadioti P, Zagouri F, Bobos M, Sotiropoulou M, Papoudou-Bai A, Chrisafi S, Efstratiou I, Aravantinos G, Nicolaou I, Gogas H, Visvikis A, Christodoulou C, Petraki C, Koutras A, Psyrri A, Pectasides D, Fountzilas G. Prognostic significance of CD8+ tumor-infiltrating lymphocytes (TILs) in patients with early breast cancer (EBC) treated with dose-dense sequential adjuvant chemotherapy (dds-CT). An observational study (ACTRN12616001043426) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-08-13.
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- 2019
11. Genotyping KRAS and EGFR Mutations in Greek Patients With Non-small-cell Lung Cancer: Incidence, Significance and Implications for Treatment
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Kotoula, Ioannis Efstratiou, E Res, Sofia Lampaki, Paris Kosmidis, Despoina Televantou, Kyriaki Papadopoulou, G. Fountzilas, Emily Daskalaki, X. Mavropoulou, Grigorios Rallis, H. Linardou, Karavasilis, Samantas E, Anna Kalogera-Fountzila, Dimitrios Pectasides, Kostas N. Syrigos, George Kouvatseas, Thomas Zaramboukas, and Mountzios G
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Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Genotyping Techniques ,medicine.disease_cause ,Biochemistry ,Disease-Free Survival ,Proto-Oncogene Proteins p21(ras) ,03 medical and health sciences ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Genotype ,Genetics ,medicine ,Humans ,Lung cancer ,neoplasms ,Molecular Biology ,Genotyping ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Incidence (epidemiology) ,Histology ,Middle Aged ,medicine.disease ,digestive system diseases ,respiratory tract diseases ,ErbB Receptors ,Survival Rate ,030220 oncology & carcinogenesis ,Mutation ,Adenocarcinoma ,Female ,Non small cell ,KRAS ,business ,Research Article ,Follow-Up Studies - Abstract
Background/Aim: KRAS mutations are reported in 20-25% of non-small cell lung cancer (NSCLC) and their prognostic role is unclear. We studied KRAS and EGFR genotyping in Greek NSCLC patients. Patients and Methods: KRAS and EGFR genotypes were centrally evaluated in 421 NSCLC patients (diagnosed September 1998 -June 2013) and associated with clinicopathological parameters. Outcome comparisons were performed in 288 patients receiving first line treatment. Results: Most patients were male (78.6%), >60 years old (63.9%), current smokers (51.1%), with adenocarcinoma histology (63.9%). EGFR and KRAS mutations were found in 10.7% and 16.6% of all histologies, respectively, and in 14.9% and 21.9% of adenocarcinomas. At 4.5 years median follow-up, KRAS status was an independent negative prognostic factor for overall survival (OS, p=0.016). KRAS mutations conferred 80% increased risk of death in patients receiving first-line treatment (p=0.002). Conclusion: The presence of KRAS mutations is an independent negative prognosticator among Greek NSCLC patients and an independent response predictor to first line treatment.
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- 2019
12. Opposite Prognostic Impact of Single PTEN-loss andPIK3CAMutations in Early High-risk Breast Cancer
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Amanda Psyrri, Ioannis Efstratiou, Flora Zagouri, Alexandra Papoudou-Bai, Christos Christodoulou, Dimitrios Pectasides, Mattheos Bobos, Eleni Giannoulatou, Vassiliki Kotoula, Ioannis Kostopoulos, George Fountzilas, Kyriaki Papadopoulou, Eleni Vrettou, Georgios Lazaridis, George Pentheroudakis, Maria Sotiropoulou, Helen Gogas, Eleni Timotheadou, Kyriaki Manousou, and Angelos Koutras
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Oncology ,Cancer Research ,medicine.medical_specialty ,Concordance ,Disease ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Trastuzumab ,Internal medicine ,Genetics ,Medicine ,PTEN ,neoplasms ,Molecular Biology ,PI3K/AKT/mTOR pathway ,biology ,business.industry ,Cancer ,medicine.disease ,030220 oncology & carcinogenesis ,biology.protein ,Immunohistochemistry ,business ,medicine.drug - Abstract
BACKGROUND/AIM: PTEN-loss and PIK3CA mutations have been addressed as markers of PI3K activation in breast cancer. We evaluated these markers in early high-risk breast cancer (EBC) focusing on PTEN immunohistochemistry (IHC) issues, particularly in HER2-positive disease. MATERIALS AND METHODS: We examined PTEN-loss and PIK3CA mutations in 1265 EBC patients treated with adjuvant chemotherapy within two clinical trials. Two different methods for the evaluation of PTEN IHC were used, one upfront binary (loss; no-loss) and the other initially multi-scale allowing for the classification of "grey zone" tumors with low and very low PTEN protein expression. RESULTS: PTEN-loss (33.4% and 22.1%, depending on the IHC method) and PIK3CA mutations (29.6%) were associated with ER/PgR/HER2-negative and ER/PgR-positive disease, respectively. Concordance of the two IHC methods was moderate (Cohen's kappa 0.624). PTEN-loss discrepancy and intra-tumor heterogeneity concerned "grey zone" tumors that were prevalent among HER2-positive cancers. PTEN-loss independently conferred higher risk for relapse and death. Compared to single PIK3CA mutations,single PTEN-loss was independently associated with increased risk for relapse and death. Depending on the evaluation method, in HER2-positive cancer, PTEN-loss was without- or of marginal unfavorable prognostic significance. CONCLUSION: In EBC, PTEN-loss is an independent predictor of poor outcome. When occurring singly, PTEN-loss and PIK3CA mutations have opposite prognostic impact. In HER2-positive disease, assessment of PTEN-loss by IHC appears unreliable and the marker is without clear prognostic significance.
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- 2019
13. Prognostic significance of tumor genotypes and CD8+ infiltrates in stage I-III colorectal cancer
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Kyriaki Papadopoulou, Vassiliki Kotoula, Ioannis Tikas, Dimitrios Pectasides, Christos Christodoulou, Gerasimos Aravantinos, Christos Poulios, Georgia-Angeliki Koliou, George Papatsibas, George Pentheroudakis, George Fountzilas, Sofia Chrisafi, Elena Fountzilas, Ioannis Efstratiou, Ioannis Varthalitis, Kleo Papaparaskeva, Kyriaki Manousou, George K. Koukoulis, Vasilios Karavasilis, Amanda Psyrri, and Georgios K. Glantzounis
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,ARID1A ,Colorectal cancer ,Lymphocyte ,03 medical and health sciences ,0302 clinical medicine ,Immunophenotyping ,Internal medicine ,Genotype ,medicine ,targeted NGS ,Clinical significance ,business.industry ,CD8 ,BRCA1 ,medicine.disease ,MMR ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,DNA mismatch repair ,business ,Research Paper - Abstract
Background We explored the clinical significance of tumor genotypes and immunophenotypes in non-metastatic colorectal cancer (CRC). Methods In primary tumors (paraffin blocks) from 412 CRC patients treated with adjuvant chemotherapy, we examined pathogenic mutations (panel NGS; 347 informative); mismatch repair (MMR) immunophenotype (360 informative); and CD8+ lymphocyte density (high – low; 412 informative). The primary outcome measure was disease-free survival (DFS). Results We evaluated 1713 pathogenic mutations (median: 3 per tumor; range 0-49); 118/412 (28.6%) tumors exhibited high CD8+ density; and, 40/360 (11.1%) were MMR-deficient. Compared to MMR-proficient, MMR-deficient tumors exhibited higher CD8+ density (chi-square, p
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- 2018
14. Multisite Tumor Sampling Reveals Extensive Heterogeneity of Tumor and Host Immune Response in Ovarian Cancer
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George Fountzilas, Sofia Chrisafi, Georgia-Angeliki Koliou, Ioannis Efstratiou, Sotirios Lakis, Vassiliki Kotoula, Alexios Papanikolaou, and Pantelis Zebekakis
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Adult ,Cancer Research ,medicine.medical_specialty ,Stromal cell ,Lymphocyte ,Biopsy ,H&E stain ,Biochemistry ,Gastroenterology ,Genetic Heterogeneity ,Immune system ,Lymphocytes, Tumor-Infiltrating ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Genetics ,medicine ,Tumor Microenvironment ,Humans ,Sampling (medicine) ,Molecular Biology ,Neoplasm Staging ,Retrospective Studies ,Ovarian Neoplasms ,medicine.diagnostic_test ,business.industry ,Ovary ,Histology ,Cytoreduction Surgical Procedures ,Middle Aged ,medicine.disease ,Prognosis ,Progression-Free Survival ,medicine.anatomical_structure ,Treatment Outcome ,Chemotherapy, Adjuvant ,Disease Progression ,Female ,business ,Ovarian cancer ,Follow-Up Studies ,Research Article - Abstract
Background/Aim: Ovarian cancer (OVCA) is characterized by genomic/molecular intra-patient heterogeneity (IPH). Tissue histology and morphological features are surrogates of the underlying genomic/molecular contexture. We assessed the morphological IPH of OVCA tumor compartments and of lymphocytic infiltrates in multiple matched samples per patient. Materials and Methods: We examined 294 hematoxylin & eosin (H&E) OVCA tumor whole sections from 70 treatment-naïve patients who had undergone cytoreductive surgery. We assessed morphological subtypes as immunoreactive (IR), solid – proliferative (SD), papilloglandular (PG), and mesenchymal transition (MT); subtype load per patient; stromal tumor-infiltrating lymphocyte (sTIL) density as average per sample; and, as maximal sTIL values (max-TILs) among all samples per patient, ovaries and implants. Results: Among all 294 tumor sections, the most frequent primary morphological subtype was PG (n=150, 51.0%), followed by MT (71, 24.1%), SD (48, 16.3%) and IR (15, 5.1%). Subtype combinations were observed in 67/294 sections (22.8%) and IPH in 48/70 patients (68.6%). PG prevailed in ovaries (p
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- 2020
15. A 55-year old male with a right fronto-parietal lesion
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Dimitrios Kanakis, Sotiris Sotiriou, Stella Chondromatidou, Stavroula Pervana, and Ioannis Efstratiou
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Male ,business.industry ,Brain Neoplasms ,General Neuroscience ,Anatomy ,Fibroma ,Middle Aged ,Fronto parietal ,Pathology and Forensic Medicine ,Frontal Lobe ,Lesion ,Text mining ,Parietal Lobe ,medicine ,Humans ,Neurology (clinical) ,medicine.symptom ,business ,Cases of the Month - Published
- 2020
16. PTTG-1 (Securin) immunoexpression in meningiomas correlates with tumor grade and proliferation rate: potential use as a diagnostic marker of malignancy
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Ioannis Efstratiou, Nicolaos A. Flaris, Alexandros Iliadis, Dimitrios Kanakis, Stavroula Pervana, Maria Aikaterini Virvili, Maria Grigoriou, G. Tripsianis, and Elissabet Pazarli
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0301 basic medicine ,Microbiology (medical) ,Mitotic index ,Pituitary Tumor Transforming Gene ,Mitosis ,Malignancy ,Pathology and Forensic Medicine ,Meningioma ,03 medical and health sciences ,Tumor grade ,0302 clinical medicine ,Biomarkers, Tumor ,Meningeal Neoplasms ,medicine ,Humans ,Immunology and Allergy ,Cell Proliferation ,biology ,business.industry ,General Medicine ,medicine.disease ,Gene Expression Regulation, Neoplastic ,Securin ,Ki-67 Antigen ,030104 developmental biology ,030220 oncology & carcinogenesis ,Ki-67 ,biology.protein ,Cancer research ,Immunohistochemistry ,business - Abstract
This study essentially aims to contribute to the immunohistochemical investigation of the use of pituitary tumor transforming gene (PTTG) as a marker of cell proliferation or advanced tumor grade in meningiomas of various WHO grades. In all, 51 cases were recovered in total, 21 Grade-I, 23 Grade-II and 7 Grade-III meningiomas. Mitotic index (MI), Ki-67/MiB-1 positivity percentage and PTTG expression were analyzed in correlation to each other as well as to the tumor WHO grades. All three biomarkers showed a high diagnostic significance and a strong association with WHO grades. In comparison, PTTG expression was on a par with the other two indices, and performed very well regarding identification of advanced grade tumors. PTTG may be considered an important diagnostic tool and serve in the future as a novel prognosticator of the biological behavior of all grade meningiomas as well as a useful high-risk patient selection tool.
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- 2018
17. Abstract P6-09-07: Mutation characteristics and tumor infiltrating lymphocytes in early and metastatic HER2-positive breast cancer
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Georgios Pentheroudakis, Flora Zagouri, George Kouvatseas, Ioannis Tikas, Eleftheria Tsolaki, Dimitrios Pectasides, Pavlos Papakostas, Christos Christodoulou, Angelos Koutras, Mattheos Bobos, G. Fountzilas, PA Kosmidis, Elpida Charalambous, Georgios Lazaridis, Vasiliki Kotoula, Eleni Giannoulatou, and Ioannis Efstratiou
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Gynecology ,Cancer Research ,medicine.medical_specialty ,Oncology ,Tumor-infiltrating lymphocytes ,business.industry ,HER2 Positive Breast Cancer ,Mutation (genetic algorithm) ,medicine ,Cancer research ,business - Abstract
Background-aim: HER2-positive breast cancer (BC) features high rates of tumor infiltrating lymphocytes (TILs) and mutations (mut) in various genes, more frequently in TP53. We investigated associations between TILs and mutations in HER2-positive BC and their impact on patient outcome in early and metastatic BC (EBC and MBC, respectively), which remain largely unexplored. Methods:In 352 primary paraffin tumors from patients with HER2-positive disease, we examined amino acid changing mutations (20% variant frequency). Study groups were: (A) 218 EBC, including 117 patients treated with adjuvant chemotherapy only (CT) and 101 patients treated with CT and trastuzumab (CTT); (B) 134 MBC, including 95 patients who relapsed upon adjuvant CT without trastuzumab (R-MBC) and 39 patients who were first diagnosed with metastatic disease (de novo MBC). TILs were assessed as percentage of stromal tumor area. Clinical endpoints were disease-free survival in 5 years (5yr DFS) for EBC, and time-to-progression (TTP) from 1st line CTT treatment start for MBC. Results: 243/352 tumors (69%) carried at least one mut; 27/352 (8%) of tumors >10 up to 150 mut (hypermut); 192/352 (54%) at least one possibly clonal mut. Mean mut number and TP53 mut in particular were highest in R-MBC and lowest in EBC; mean TILs density followed the opposite pattern (all p3 compared to 0-3 positive nodes (OR 3.83, CI 1.76-8.34, p=0.001); lower risk for relapse was observed for higher TILs irrespectively of treatment (OR 0.93, CI 0.90-0.97, p=0.001), for TP53 mut (OR 0.39, CI 0.18-0.87, p=0.022) and for clonal TP53 mut in CTT-treated patients (OR 0.10, CI 0.02-0.58) but not in CT-treated patients (interaction p=0.084). The presence of any clonal mut (hazard ratio [HR] 2.77, CI 1.42-5.38) and of clonal TP53 mut (HR 2.24, CI 1.20-4.17) conferred worse TTP in de novo but not in R-MBC; these interactions remained significant upon multivariate analysis (interaction p=0.007 and p=0.061, respectively). Higher TILs in the absence of clonal mut conferred longer TTP (HR 0.75, CI 0.56-0.99) but no such effect was observed for tumors with clonal mut (multivariate interaction p=0.052). Classic independent predictors of unfavorable TTP in MBC were younger age (p=0.002), absence of hormone receptors (p=0.001) and poor performance status (p=0.044). PIK3CA mut did not remain significant in any of the examined settings. Conclusions: The expected pattern of higher TILs associated with mutation number and clonality was not observed in HER2-positive BC; the favorable effect of TILs only in the absence of clonal mut in MBC may imply exhausted immune response. Clonal TP53 mut may serve as a predictor for trastuzumab benefit in EBC but as an adverse prognosticator in trastuzumab-treated de novo MBC, which, if further validated, is of potential clinical relevance.Background-aim: HER2-positive breast cancer (BC) features high rates of tumor infiltrating lymphocytes (TILs) and mutations (mut) in various genes, more frequently in TP53. We investigated associations between TILs and mutations in HER2-positive BC and their impact on patient outcome in early and metastatic BC (EBC and MBC, respectively), which remain largely unexplored. Methods:In 352 primary paraffin tumors from patients with HER2-positive disease, we examined amino acid changing mutations (20% variant frequency). Study groups were: (A) 218 EBC, including 117 patients treated with adjuvant chemotherapy only (CT) and 101 patients treated with CT and trastuzumab (CTT); (B) 134 MBC, including 95 patients who relapsed upon adjuvant CT without trastuzumab (R-MBC) and 39 patients who were first diagnosed with metastatic disease (de novo MBC). TILs were assessed as percentage of stromal tumor area. Clinical endpoints were disease-free survival in 5 years (5yr DFS) for EBC, and time-to-progression (TTP) from 1st line CTT treatment start for MBC. Results: 243/352 tumors (69%) carried at least one mut; 27/352 (8%) of tumors >10 up to 150 mut (hypermut); 192/352 (54%) at least one possibly clonal mut. Mean mut number and TP53 mut in particular were highest in R-MBC and lowest in EBC; mean TILs density followed the opposite pattern (all p3 compared to 0-3 positive nodes (OR 3.83, CI 1.76-8.34, p=0.001); lower risk for relapse was observed for higher TILs irrespectively of treatment (OR 0.93, CI 0.90-0.97, p=0.001), for TP53 mut (OR 0.39, CI 0.18-0.87, p=0.022) and for clonal TP53 mut in CTT-treated patients (OR 0.10, CI 0.02-0.58) but not in CT-treated patients (interaction p=0.084). The presence of any clonal mut (hazard ratio [HR] 2.77, CI 1.42-5.38) and of clonal TP53 mut (HR 2.24, CI 1.20-4.17) conferred worse TTP in de novo but not in R-MBC; these interactions remained significant upon multivariate analysis (interaction p=0.007 and p=0.061, respectively). Higher TILs in the absence of clonal mut conferred longer TTP (HR 0.75, CI 0.56-0.99) but no such effect was observed for tumors with clonal mut (multivariate interaction p=0.052). Classic independent predictors of unfavorable TTP in MBC were younger age (p=0.002), absence of hormone receptors (p=0.001) and poor performance status (p=0.044). PIK3CA mut did not remain significant in any of the examined settings. Conclusions: The expected pattern of higher TILs associated with mutation number and clonality was not observed in HER2-positive BC; the favorable effect of TILs only in the absence of clonal mut in MBC may imply exhausted immune response. Clonal TP53 mut may serve as a predictor for trastuzumab benefit in EBC but as an adverse prognosticator in trastuzumab-treated de novo MBC, which, if further validated, is of potential clinical relevance. Citation Format: Kotoula V, Giannoulatou E, Kouvatseas G, Tikas I, Lazaridis G, Charalambous E, Efstratiou I, Bobos M, Tsolaki E, Zagouri F, Christodoulou C, Pentheroudakis G, Koutras A, Papakostas P, Kosmidis PA, Pectasides D, Fountzilas G. Mutation characteristics and tumor infiltrating lymphocytes in early and metastatic HER2-positive breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-07.
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- 2017
18. Abstract P5-08-50: Associations of MYC protein expression and gene status with breast cancer subtypes and outcome in patients treated with anthracycline-based adjuvant chemotherapy
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Anna Goussia, Ioannis Efstratiou, Triantafyllia Koletsa, Kitty Pavlakis, G. Fountzilas, Kalliopi Petraki, Maria Sotiropoulou, Helen Gogas, Zoi Alexopoulou, Georgios Pentheroudakis, Eleni Timotheadou, Eleftheria Tsolaki, Angelos Koutras, Anna Batistatou, Vasiliki Kotoula, E. Razis, Maria Karina, and Mattheos Bobos
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Oncology ,Cancer Research ,Polysomy ,medicine.medical_specialty ,Pathology ,Tissue microarray ,Anthracycline ,medicine.diagnostic_test ,business.industry ,Cancer ,medicine.disease ,chemistry.chemical_compound ,Breast cancer ,Paclitaxel ,chemistry ,Internal medicine ,medicine ,Biomarker (medicine) ,business ,Fluorescence in situ hybridization - Abstract
Background-Aim: Breast cancer is a heterogeneous disease and despite recent scientific progress there is still need for the identification of biomarkers associated with risk for relapse, as well as for markers identifying patients who will benefit from specific treatments. The aim of the present study was to investigate the role of MYC, as a clinically meaningful biomarker, in the outcome of breast cancer subtypes. Patients and Methods: We have pooled the patients and the respective breast carcinomas from two randomized anthracycline-based adjuvant phase III trials, consecutively conducted by the Hellenic Cooperative Oncology Group (HE10/97 and HE10/00). The HE10/97 trial included a non-paclitaxel arm. Tissue microarrays were constructed from 1,060 formalin-fixed paraffin-embedded tumor tissue samples that were collected retrospectively in the first and prospectively in the second trial. MYC was evaluated by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in 986 cases. Results: In total 61.0% of the cases showed positive cytoplasmic MYC immunostaining, while 26.5% showed positive nuclear staining. 65-80% of the patients were characterized as non-amplified or loss/normal-low gain in all FISH cut-offs examined. A weak association was observed between FISH and nuclear protein expression of MYC. High histological grade was associated with MYC protein overexpression and gene amplification. In terms of disease-free survival (DFS), low (2.5-5 copies) and high (≥5 copies) gain of MYC was of adverse prognostic value compared to loss/normal ( Treatment with paclitaxel was found to differentiate the effect of MYC: CEP8 ratio ≥1.3 and polysomy 8 in terms of DFS and OS in our total cohort. Among patients with CEP8 ratio ≥1.3 and polysomy 8, those treated with paclitaxel performed significantly better than those not treated, while among patients not treated with paclitaxel, those with CEP8 ratio ≥1.3 and polysomy 8 performed much worse than those with CEP8 ratio Conclusions: Our data suggest that MYC has prognostic and predictive value in patients with breast cancer. MYC amplification and MYC protein overexpression are detected in breast cancer patients and are of adverse prognostic value for DFS and OS. Polysomy 8 is also associated with worse prognosis. Treatment with paclitaxel in the adjuvant setting benefits breast cancer patients with MYC:CEP8 ratio ≥1.3 and polysomy 8. Citation Format: Batistatou A, Razis E, Bobos M, Tsolaki E, Timotheadou E, Alexopoulou Z, Goussia A, Gogas H, Koutras A, Karina M, Pentheroudakis G, Efstratiou I, Petraki K, Sotiropoulou M, Pavlakis K, Koletsa T, Kotoula V, Fountzilas G. Associations of MYC protein expression and gene status with breast cancer subtypes and outcome in patients treated with anthracycline-based adjuvant chemotherapy. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-50.
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- 2016
19. Pathogenic BRCA1 mutations may be necessary but not sufficient for tissue genomic heterogeneity: Deep sequencing data from ovarian cancer patients
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Alexios Papanikolaou, Ioannis Tikas, Ioannis S. Vlachos, Ioannis Efstratiou, Georgios Lazaridis, Basil C. Tarlatzis, Florentia Fostira, Eleni Giannoulatou, Vassiliki Kotoula, Sotirios Lakis, Kyriaki Manoussou, Kyriaki Papadopoulou, and George Fountzilas
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0301 basic medicine ,Adult ,animal structures ,endocrine system diseases ,Genotype ,medicine.medical_treatment ,Loss of Heterozygosity ,Carcinoma, Ovarian Epithelial ,medicine.disease_cause ,Germline ,Deep sequencing ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,Humans ,Clinical significance ,In patient ,Germ-Line Mutation ,Aged ,Neoplasm Staging ,Retrospective Studies ,Aged, 80 and over ,Chemotherapy ,Mutation ,business.industry ,BRCA1 Protein ,Obstetrics and Gynecology ,High-Throughput Nucleotide Sequencing ,Middle Aged ,medicine.disease ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Female ,business ,Ovarian cancer - Abstract
Tissue genomic heterogeneity (t-HET) in patients with epithelial ovarian cancer (OVCA) is related to tissue plasticity, i.e., flexibility to adapt to adverse molecular environments. Here, we interrogated the presence and clinical relevance of OVCA t-HET.We applied high-depth (2000×) sequencing on 297 paraffin tissue samples (fallopian tubes, ovaries, intra-abdominal metastases) from 71 treatment-naïve patients who subsequently received first-line platinum-based chemotherapy. Based on tissue mutation patterns, we distinguished tissue genotypes into: no mutation (33/297 samples; 11.1%), stable (173; 58.2%) and unstable (91; 30.7%). We profiled genotypes per patient and assessed t-HET in 69 patients. Predicted pathogenic mutations refer to germline and/or tissues.Among all 71 patients, 46 (64.8%) had pathogenic BRCA1 mutations and 15 (21.7%) had BRCA1/2 disruption (i.e., pathogenic mutations with position-LOH). We classified 29 patients with t-HET (42%), all with pathogenic BRCA1; t-HET was observed in 64% with such mutations (p 0.001). As opposed to non-t-HET, matched tissues in t-HET shared pathogenic BRCA1 (p 0.001) but not BRCA2 and TP53. Germline BRCA1 mutations in tissues exhibited position-LOH; heterozygous status; or, partial loss of the inherited allele accompanied by additional clonal mutations. Patients with t-HET had worse outcome (log-rank p = 0.048 [progression-free]; p = 0.037 [overall survival]), including 12/15 patients with disrupted BRCA1/2 and 3 BRCA1 carriers with partial germline loss in tissues.Pathogenic BRCA1 mutations appear necessary but may not be sufficient for the establishment of t-HET. t-HET may be associated with worse outcome, including in patients with disrupted BRCA1/2, which is usually considered as a favourable marker. OVCA t-HET may need to be addressed for treatment decisions.
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- 2018
20. AMALTHEA: Prospective, Single-Arm Study of the Hellenic Cooperative Oncology Group (HeCOG) Evaluating Efficacy and Safety of First-Line FOLFIRI + Aflibercept for 6 Months Followed by Aflibercept Maintenance in Patients With Metastatic Colorectal Cancer
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Dimitrios Bafaloukos, Ioannis Efstratiou, Vassiliki Kotoula, Gerasimos Aravantinos, Lydia Kalogeropoulou, Ioannis Souglakos, Ioannis Tikas, Epaminontas Samantas, Georgia-Angeliki Koliou, Eleni Vrettou, Anna Kalogera-Fountzila, George Pentheroudakis, Constantina Petraki, Joseph Sgouros, Konstantinos Laschos, Alexandra Voutsina, Georgios Koumakis, Christos Poulios, Nikolaos Kentepozidis, Athina Goudopoulou, George Fountzilas, Dimitrios Pectasides, Vasilios Karavasilis, and Georgios Zarkavelis
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0301 basic medicine ,Oncology ,Adult ,Male ,medicine.medical_specialty ,Adolescent ,Recombinant Fusion Proteins ,Leucovorin ,Irinotecan ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Mucositis ,Humans ,Progression-free survival ,Prospective Studies ,Survival rate ,Aflibercept ,Aged ,Aged, 80 and over ,business.industry ,Liver Neoplasms ,Gastroenterology ,Middle Aged ,medicine.disease ,Prognosis ,Oxaliplatin ,Survival Rate ,Regimen ,030104 developmental biology ,Receptors, Vascular Endothelial Growth Factor ,030220 oncology & carcinogenesis ,FOLFIRI ,Female ,Fluorouracil ,business ,Colorectal Neoplasms ,Febrile neutropenia ,medicine.drug ,Follow-Up Studies - Abstract
The efficacy and safety of the FOLFIRI (leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin) regimen combined with aflibercept has not been studied in the first-line management of patients with metastatic colorectal cancer (mCRC).In the context of a prospective single-arm trial (NCT02129257), patients with mCRC received standard doses of a maximum of 12 cycles of FOLFIRI combined with aflibercept (4 mg/kg body weight delivered intravenously) every 2 weeks, followed by aflibercept maintenance. Endpoints were 12-month progression-free survival rate, efficacy, and toxicity.Seventy-three fit patients were enrolled onto the study between 2014 and 2016. Median relative dose intensities administered were 0.80 for irinotecan and 1.0 for aflibercept. The most common grade 3/4 adverse events were neutropenia (13 patients, 18%), febrile neutropenia (3 patients, 4%), diarrhea (11 patients, 15%), hypertension (19 patients, 26%), proteinuria (8 patients, 11%), infections (8 patients, 11%), and mucositis (6 patients, 8%), with no toxic deaths. The objective response rate was 46.6%, significantly associated with the presence of right-sided primary, synchronous metastases, and a relapse-free interval of 12 months (odds ratio = 3.00, 2.92, and 3.75 respectively, P ≤ .05). Intermediate infiltration by stromal core lymphocytes correlated with progression-free survival (hazard ratio = 0.40, [95% confidence interval (CI), 0.19-0.83], P = .014). At a median follow-up of 24.5 months, 12-month progression-free survival rate was 21.9% (median overall survival 20.9 months [95% CI, 16.6-29], median progression-free survival 8.4 months [95% CI, 7.4-9.3]).The FOLFIRI + aflibercept regimen is active and tolerable; however, it failed to improve historical benchmarks of efficacy in chemonaive patients with mCRC. Preliminary data hint that this regimen has cytoreductive activity in disease with adverse biology.
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- 2018
21. Abstract P3-09-07: Prognostic value of immunophenotypically defined subtypes in patients treated with dose-dense sequential adjuvant chemotherapy in the trastuzumab era. A Hellenic Cooperative Oncology Group study
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Ioannis Efstratiou, George Fountzilas, Sofia Chrisafi, Anna Batistatou, Olympia Tzaida, Eleni Timotheadou, Petroula Arapantoni-Dadioti, Flora Zagouri, Triantafyllia Koletsa, Sotiris Lakis, Dimitrios Pectasides, Georgia Gourgioti, Eleftheria Tsolaki, Alexandra Papoudou-Bai, Mattheos Bobos, Helen Gogas, and Elena Fountzilas
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Oncology ,Cancer Research ,medicine.medical_specialty ,Tissue microarray ,business.industry ,Estrogen receptor ,Cancer ,medicine.disease ,Basal (phylogenetics) ,Cytokeratin ,Breast cancer ,Trastuzumab ,Internal medicine ,Progesterone receptor ,medicine ,skin and connective tissue diseases ,business ,medicine.drug - Abstract
Background-Aim: The aim of the present study was to explore the efficacy of dose-dense sequential adjuvant chemotherapy followed by trastuzumab in HER2-positive patients according to the immunohistochemically (IHC) defined subtypes. Patients and methods: A total of 771 formalin-fixed paraffin-embedded (FFPE) tumor tissue samples, prospectively collected from 990 eligible patients with high-risk N0 or N1 operable breast cancer participating in a phase III trial (HE10/05), were centrally assessed in tissue microarrays by IHC for 6 biological markers, that is, estrogen receptor (ER), progesterone receptor (PgR), HER2, Ki67, cytokeratin 5 (CK5) and EGFR. All cases were further evaluated for HER2 amplification by FISH. Patients were classified as: luminal A (ER/PgR-positive, HER2-negative, Ki67low, N=382, 49.5%); luminal B (ER/PgR-positive, HER2-negative, Ki67high, N=136, 17.6%); luminal-HER2 (ER/PgR-positive, HER2-positive, N=125, 16.2%); HER2-enriched (ER-negative, PgR-negative, HER2-positive, N=63, 8.2%); triple-negative (TNBC) (ER-negative, PgR-negative, HER2-negative, N=65, 8.4%); and basal core phenotype (BCP) (TNBC, CK5-positive and/or EGFR-positive, N=53, 6.9%). Results: At a median follow-up of 60.5 months, the 3-year disease-free survival (DFS) and overall survival (OS) rates for the total patient population were 88.3% and 96.0%, respectively. The 3-year DFS rates for luminal A, luminal B, luminal-HER2, HER2-enriched, TNBC and BCP patients were 91.1%, 88.2%, 86.4%, 93.7%, 87.7%, and 89.4%, respectively, while the corresponding 3-year OS rates were 95.8%, 95.6%, 97.6%, 95.2%, 95.4%, and 95.0%, respectively. No significant differences were detected for either 3-year DFS or OS in the immunohistochemically defined subtypes, except a trend for significantly worse DFS in patients with luminal-HER2 tumors compared to patients with HER2-enriched tumors (log-rank, p=0.069). Conclusions: In the post-trastuzumab era, at a relatively short follow-up, the luminal-HER2 patients show a trend for worse DFS compared to patients with HER2-enriched tumors treated with dose-dense sequential adjuvant chemotherapy followed by trastuzumab. No other significant differences were detected, with follow-up however being continued. Citation Format: George Fountzilas, Eleni Timotheadou, Georgia Gourgioti, Petroula Arapantoni-Dadioti, Sotiris Lakis, Anna Batistatou, Triantafyllia Koletsa, Olympia Tzaida, Mattheos Bobos, Alexandra Papoudou-Bai, Eleftheria Tsolaki, Sofia Chrisafi, Elena Fountzilas, Ioannis Efstratiou, Helen Gogas, Flora Zagouri, Dimitrios Pectasides. Prognostic value of immunophenotypically defined subtypes in patients treated with dose-dense sequential adjuvant chemotherapy in the trastuzumab era. A Hellenic Cooperative Oncology Group study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-09-07.
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- 2015
22. Abstracts from the 4th World Congress of the International Dermoscopy Society, April 16-18, 2015, Vienna, Austria
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Michael A. Marchetti, Alexandros Stratigos, Claudia Jaeger, Nanja van Geel, Erika Varga, Rachel M Bowden, Nebojsa Pesic, Lauren A. Penn, Francesca Farnetani, Irena Walecka, Otto S. Wolfbeis, Anna Pogorzelska-Antkowiak, Małgorzata Zadurska, Miriam A. Jesús Silva, Mari Grönroos, Fabrizio Ayala, Claudia Sprincenatu, Ausilia Maria Manganoni, Jhonatan Rafael S. Pinheiro, Vincent Descamps, Era C. Murzaku, Josephine Rau, Christian Landi, Josep Malvehy, Othon Papadopoulos, Renato Talamini, Savitha L. Beergouder, Adrian Ballano Ruiz, Karina Scandura, Flavia Persechino, Yunxian Tian, Mark Berneburg, Iara Drakensjö, Luis Javier Del pozo, Elizabeth Lazaridou, Marwah A. Saleh, Wei Zhang, Dalal Mosaad, Aida Carolina Medina, Alka Lalji, Robabeh Abedini, FZ Debagh, Ligia Brzezinska-Wcislo, Nurşah Doğan, Naglaa Ahmed, Tamerlan Shaipov, Ritta Khoury, Lidija Kandolf-Sekulovic, Aldo Bono, Luis Angel Vera, Naotomo Kambe, Jaka Rados, Sergio Talarico, Milvia Maria S. E. S. Enokihara, Iris Zalaudek, Malgorzata Maj, Francesca Specchio, Paloma Arribas, Nazan Emiroglu, Andreea Ioana Popescu, Irina Sergeeva, Virginia Chitu, Michael Kirschbaum, Sergio Yamada, Niken Wulandari, Rotaru Maria, Lore Pil, Lieve Brochez, Anthony Azzi, Vasiliy Y. Sergeev, Raimonds Karls, Zeynep Topkarci, Tanja Planinsek Rucigaj, Osvania Maris, Graham J. Mann, Timótio Dorn, Lubomir Drlik, Pilar Iranzo, Sara Minghetti, Michael Noe, Ahmet R Akar, Jesus Cuevas Santos, Laura Raducu, Salim Ysmail-Dahlouk, Laura Mazzoni, Sidharth Sonthalia, Neşe Çallı Demirkan, Yaei Togawa, Branislava Gajic, Ayelet Rishpon, Chih-Hsun Yang, Barbara Boone, José Luis López-Estebaranz, Markus Albert, George Evangelou, André L.M. Oliveira, Ioana Gencia, Nada Vuckovic, Rosa Perelló, Ana Maria Draganita, Michel Colomb, Ayse Cefle, Hongguang Lu, Annarosa Virgili, Hayriye Saricaoglu, Esther A.W. Wolberink, Michael Russu, Elisabeth Arnoult-Coudoux, Caroline Nicaise-Bergère, Aleksandra M Ignjatović, Necmettin Özdemir, Kristīne Zabludovska, Cemal Bilaç, Jose Luis Lopez Estebaranz, Marie-Christine Lami, Harold S. Rabinovitz, Izabel Bota, Damien Grivet, Dimitrije Brasanac, Andrei Jalba, Joep Hoevenaars, Sofie De Schepper, Deniz Duman, Vladimir Vasku, Anna Belloni Fortina, Rosa Cristina Coppola, Marion Chavez-Bourgeois, Hoon-Soo Kim, Zamira Barragan, Julia Welzel, Thomas Ruzicka, Patricia V. Cristodor, Pierfrancesco Zampieri, Michael Lanthaler, Marc Haspeslagh, Jürgen Christian Becker, Gamze Erfan, Tanja Maier, Hui Mei Cheng, Mauro Enokihara, Ana Arance, Emel Dikicioglu Cetin, Pranaya A. Bagde, Mona M. Elfangary, Stefano Cavicchini, Alicia Barreiro, Odivânia Krüger, Mariana Petaccia Macedo, Itziar Erana Tomas, Elimar Elias Gomes, Monika Vrablova, Marcio Lorencini, Javier Alcántara González, Giuseppe Micali, Kerstin Kellermann, Mauricio Mendonca do Nascimento, Elisabeth Mt Wurm, Elena Sánchez-Largo Uceda, Yury Sergeev, Céleste Lebbé, Manfred Fiebiger, Gisele Gargantini Rezze, Antonio Graziano, Ana Pampín, Márcia Ferreira Candido, Martine Bagot, Jan Lapins, Nahide Onsun, Daniela Göppner, Katie Lee, Josef Schröder, Gisele G Rezze, Reyes Gamo, Mauricio Soto-Gamboa, Giovanni Pellacani, Maria Luiza P. Freitas, Mizuki Sawada, Hyun-Chang Ko, Ramon M Pujol Vallverdú, Jin gyoon Park, Peter Weber, Alberto Mota, Theofanis Spiliopoulos, Renata B. Marques, Daiji Furusho, Barbora Divisova, Pascale Guitera, Johan Heilborn, Alexandr Fedoseev, Athanasios Kyrgidis, Zakia Douhi, Mariame Meziane, Florent Grange, Alister Lilleyman, Juliana C. Marques-Da-Costa, Mitsuyasu Nakajima, Camilla Reggiani, Marina Meneses, Anna Sokolova, Zoe Apalla, Leo Čabrijan, Tim Lee, Piergiacomo Calzavara-Pinton, Tomas Fikrle, Georgios Chaidemenos, Braun Ralph, Aikaterini Patsatsi, Ekin Şavk, Marcela Pecora Cohen, Ioannis Efstratiou, Gurol Acikgoz, Pietro Quaglino, Nati Angelica, Luc Thomas, Edileia Bagatin, Kedima C. Nassif, Dimitrios Sotiriadis, Regina Fink-Puches, Anna Maria Wozniak, Salvador González, Agnieszka Buszko, Fezal Ozdemir, Banu Yaman, Vishnu Moodalgiri, Anne Grange, Robert J Meier, Davorin Loncaric, Fatmagül Keleş, Renato Marchiori Bakos, Sergio Chimenti, Sebastian Podlipnik, Pınar Incel Uysal, Devinder M Thappa, Nida Kaçar, Emel Bulbul Baskan, Erna Snellman, Pietro Rubegni, J. Kreusch, Hae Jin Pak, Danijela Dobrosavljevic Vukojevic, Bengü Nisa Akay, Holger A. Haenssle, Horacio Cabo, Anna Rammlmair, Fred Godtliebsen, Chiara Ferrari, Hiroshi Sakai, Christina Kemanetzi, Åsa Ingvar, Jitka Suchmannova, Zlata Janjic, Samira Zobiri, Haishan Zeng, Emine Böyük, Antonello Felli, Je-Ho Mun, Pablo Fernández Peñas, Ercan Caliskan, Satish S. Udare, Borna Pavičić, Max Hundeiker, Cristel Ruini, A. Hakan Cermik, Ülker Gül, Auro ra Parodi, Timothy P. Wu, Bernardo Gontijo, Ivan Klyuzhin, Gabriela Turcu, Sylvia Aidé Martínez-Cabriales, Francisco Alcántara Nicolás, Inge A. Krisanti, Sandra Cecilia García-García, Meriem Benfodda, Nika Madjlessi, Paraskevi Karagianni, Gizem Yağcıoğlu, Didem Dizman, Danielle I. Shitara, Nilda Eliana Gomez-Bernal, Mirna Šitum, Natalia Ilina, Job Van Der Heijden, Małgorzata Kwiatkowska, Bota Izabel, Ismini Vassilaki, Irene Potouridou, Jorge Luis Rosado, Lukas Prantl, María-José Bañuls, Fernando N. Barbosa, Seitaro Nakagawa, Jana Dornheim, Hitoshi Iyatomi, Rifat Saitburkhanov, Çiğdem Çağlayan, Natalie Ong, Stefano Gardini, Temeida Alendar, Zrinka Rendić-Miočević, Ryuhei Okuyama, Wafae Bono, Olga Warszawik-Hendzel, Danica Tiodorovic-Zivkovic, Alise Balcere, Ramazan Kahveci, Sebastian Gehmert, Herbert M. Kirchesch, Fernando Javier Pinedo, Raul Niin, Dan Savastru, Andreas Blum, Valeria Coco, Alexander C. Katoulis, Yosuke Yamamoto, Mumtaz Jabeen, Louise De Brot Andrade, Lidia Rudnicka, Pierre Wolkenstein, Fatma Pelin Cengiz, Woo-il Kim, Rainer Hofmann-Wellenhof, Tine Vestergaard, Maria Valeria B. Pinheiro, Ana Filipa Pedrosa, Caroline M. Takigami, Nilgün Bilen, Feroze Kaliyadan, Lotte Themstrup, Awatef Kelati, Katrien Vossaert, Burak Sezen, Natalia Jaimes, Olga Zhukova, Peter Jung, Nidhi Singh, Uxua Floristan, Ivette Alarcon, Michel Baccard, Flávia V. Bittencourt, Nicolas Dupin, Neslihan Şendur, Flavia Boff, Lydia Garcia Gaba, João Pedreira Duprat Neto, Caius Solovan, Byung Soo Kim, Anamaria Jović, Toshitsugu Sato, Antoni Bennassar, Ilkka Pölönen, Svetlana Rogozarski, Agnieszka Kardynał, Harald P.M. Gollnick, Anastasia Trigoni, Harvey Lui, Hiroshi Koga, Dai Ogata, Zeynep N. Saraçoğlu, Nilton B Rodrigues, Ketty Peris, Vanessa da Silva, Akira Hamada, Monica Corazza, Azmat A. Khan, Cengizhan Erdem, Victor Desmond Mandel, Sabina Zurac, Laura Elena Barbosa-Moreno, Filomena Azevedo, Matsue Hiroyuki, Philippe Saiag, Kara Shah, Stephen W. Dusza, Margaret Song, Francesca Giusti, Lidija Zolotarevski, Romain Vie, Rutao Cui, Aylin Okçu Heper, Kerstin Wöltje, Kyoko Tonomura, Charlotte H. Vuong, Moira Ragazzi, Marta Andreu Barasoain, Stephan Schreml, Branka Marinović, Mona R E Abdel Halim, Selimir Kovacevic, Noriaki Kamada, Adriana Garcia-Herrera, Ayse S. Filiz, Helena Collgros, Joan A. Puig-Butille, Ulvi Loite, Meng-Tsan Tsai, Nele Degryse, Philipp Tschandl, Seiichiro Wakabayashi, Korina Tzima, Kari Nielsen, Edith Arzberger, Alain Archimbaud, Makiko Miyamoto, Steffen Emmert, Katharine Hanlon, Stefano Astorino, Andre Sobiecki, Trevino A Pakasi, Giovanni Ghigliotti, Arzu Karataş Toğral, Sara Bassoli, Mahdi Akhbardeh, Martina Ulrich, Mirna Bradamante, Gökhan Uslu, Ross Flewell-Smith, Mauro Alaibac, Bettina Kranzelbinder, Steven Gazal, Nina Malishevskaya, Mikhail Ustinov, Noora Neittaanmäki-Perttu, Olga Simionescu, Saime Irkoren, Mahsa Ansari, Mustafa Turhan Sahin, Priit Kruus, Jana Janovska, Vesna Gajanin, Giovanni Ponti, Alon Scope, Ozkan Kanat, Cesare Massone, Thomas Schopf, Karolina Hadasik, Magnus Karlsson, Ayça Tan, Ignacio Gómez Martín, Armand Bensussan, Dilara Tüysüz, Saleh M. H. El Shiemy, Ine De Wispelaere, Malou Peppelman, Kenan Aydogan, Christian Teutsch, Ryszard A. Antkowiak, Nathalie De Carvahlo, Fatma Shabaka, Matthias Karasek, Christina Fotiadou, Wael M. Saudi, Matthias Weber, Maria Saletta Palumbo, Elisa Benati, Hana Helppikangas, Mariana Grigore, Leonard Witkamp, Rajiv Kumar, Stella Atkins, Eugene Y. Neretin, Dirk Berndt, Piet E.J van Erp, Alessandro Testori, David Duffy, Steluta Ratiu, Tara Bronsnick, Christoph Rinner, Soo-Han Woo, Federica Ferrari, Gabriela Garbin, Eduardo Nagore, Claus Duschl, Caterina Longo, Daniel Alcala-Perez, Helmut Beltraminelli, Sarah Hedtrich, David C McLean, Bojana Spasic, Martin Laimer, Malgorzata Pawlowska-Kisiel, Bohdan Lytvynenko, Heba I. Nagy Abd El-Gawad, Jean-Luc Perrot, Daška Štulhofer Buzina, Dimitrios Rigopoulos, Christian Hallermann, Jeffrey Keir, Adriana Martín Fuentes, Franz Trautinger, Walter L. G. Machado, Emese Gellén, Tatjana Ros, Gabriella Emri, Pinar Y. Basak, Nilay Duman, Reinhart Speeckaert, Peter Komericki, Maciel Zortea, Raphaela Kaestle, Lucía Pérez Carmona, Masaru Tanaka, Ionela Manole, Calin Giurcaneanu, Cristina Carrera, Jianhua Zhao, Marsha Mitchum, Isil Kilinc Karaarslan, Michael Muntifering, Alice Casari, Nicole Basset-Seguin, Seok-Kweon Yun, Vesna Mikulic, Albert Brugués, Kim-Dung Nguyen, Reshmi Madankumar, Joo-Ik Kim, Anna Skrok, Nicolle Mazzotti, Aomar Ammar-Khodja, Alina Avram, Laxmisha Chandrashekar, Dilek Biyik Ozkaya, Refika F. Artuz, Joanna Czuwara-Ladykowska, Hana Szakos, Dejan M Nikolic, Katarzyna Żórawicz, Georg Duftschmid, Natalia Pikelgaupt, Jorge Ocampo-Candiani, Irdina Drljevic, Canten Tataroglu, Esther Jiménez Blázquez, Philippe Gain, Simonetta Piana, Yunus Bulgu, Lars Dornheim, Bruno Labeille, Helmut Schaider, Nitul Khiroya, Sofia Theotokoglou, Christian Morsczeck, Kalliopi Armyra, Serap Öztürkcan, Shricharit h Shetty, Ozlem Su, Susana Puig, Lina Ivert, Katia Ongenae, Hirotsugu Shirabe, Ardalan Benam, Gustav Christensen, Veronika Paťavová, Adria Gual, Laura Pavoni, Mihaita Viorica Mihalceanu, Slobodan Jesic, Abdurrahman Bugra Cengiz, Jerome Becquart, Yasutomo Mikoshiba, Mattia Carbotti, Marcelo O. Samolé, Margherita Raucci, Sven Lanssens, Maria João M. Vasconcelos, Valeriy Semisazhenov, Fabio Facchetti, Monia Maccaferri, Vincenzo Panasiti, Camila M. Carvalho, Elena Tolomio, Ercan Arca, Celia Badenas, Sonia Segura Tigell, Francesco Lacarrubba, Ruzica Jurakic Toncic, Uday Khopkar, Uwe Seidl, Clóvis Antônio Lopes Pinto, Alice Marneffe, Zhenguo Wu, Josefin Lysell, Malgorzata Olszewska, Marta Ruano Del Salado, Alina Gogulescu, Tarl W. Prow, Christine Fink, Jean-Marie Tan, Milana Ivkov Simic, Mahshid S. Ansari, Stamatina Geleki, Sondang P. Sirait, Flavia Baderca, Marcella N. Silva, Andra Pehoiu, Joost Koehoorn, Ajay Goyal, Maria Dirlei Ferreira de Souza Begnami, Hui-bin Lu, Hoda A. Moneib, Maria Antonietta Pizzichetta, Scott Menzies, Gulsel Anil Bahali, Vesna Tlaker Zunter, Elfrida Carstea, Ines Chevolet, Septimiu Enache, Aysun Şikar Aktürk, Clara Kirchner, Greg Canning, Dina M. Shahin, Incilay Kalay Tugrul, Kristina Opletalova, Lars Hofmann, Mario Santinami, Anna Elisa Verzì, Asunción Vicente, Nathalia Delcourt, null Mernissi, Duru Tabanlıoglu Onan, Dorothy Polydorou, Irma Korom, Sara Moreno Fernández, Salim Gallouj, Annamari Ranki, Riina Hallik, Saduman Balaban Adim, Erietta Christofidou, Gustavo D. C. Dieamant, Vincenzo De Giorgi, Gregor B.E. Jemec, Kajsa Møllersen, Monisha lalji, Georgiana Simona Mohor, Hans-Jürgen Schulz, Justin R Sharpe, Karinna S. Machado, Efterpi Demiri, Mohammed I. AlJasser, Jelena Stojkovic-Filipovic, Harald Kittler, José M. A. Lopes, Adriana Diaconeasa, Patricia Serrano, Alfonso D’Orazio, Luca Mazzucchelli, Riccardo Bono, Oliver Felthaus, Juan Garcias-Ladaria, Zeljko Mijuskovic, Zsuzsanna Bago-Horvath, Alin Laurentiu Tatu, Christine Prodinger, Roland Blum, Demetrios Ioannides, Nadem Soufir, Diego Serraino, Ahmed M. Sadek, Leticia Calzado Villareal, Elliot Coates, Mariana Costache, Machuel Bruno, Bengu Gerceker Turk, Liliana Gabriela Popa, Han-Uk Kim, Lisa Hoogedoorn, Efstratios Vakirlis, Monika Kotrlá, Gabriel Salerni, Ela Comert, Salvatore Zanframundo, Zsuzsanna Lengyel, Francisco Jose Deleon, Maryam Sadeghi Naeeni, Georgios Kontochristopoulos, Ana Carolina Cherobin, Michiyo Matsumoto-Nakano, Gabriela Fortes Escobar, Maria Concetta Fargnoli, Ayse Oktem, Petra Fedorcova, Slavomir Urbancek, Hyunju Jin, Frédéric Cambazard, Tracey Newlove, Nataliya Sirmays, Cliff Rosendahl, Tamara Micantonio, Shirin Bajaj, Masa Gorsic, Ana Carolina L. Viana, Valentin Popa, Hubert Pehamberger, Anna Maria Carrozzo, Valentina Girgenti, Phil McClenahan, Beata Bergler-Czop, Alex Llambrich, Özgür Bakar, David Polsky, Krishnakant B. Pandya, Andrea Maurichi, Isabelle Hoorens, Paola Sorgi, Marianne Niin, Serena Magi, Malathi Munisamy, Zlatko Marušić, Cristina Mangas, Hakan Yesil, Miriam Potrony, Safaa Y. Negm, Maria T. Corradin, Stefania Seidenari, Işıl Bulur, Evelin Csernus, Gemma Tell-Marti, Alix Thomas, Juliana Casagrande Tavoloni Braga, Marco Manfredini, Karime M. Hassun, Celia Levy-Silbon, Lali Mekokishvili, Cem Yildirim, Hanna Eriksson, John H. Pyne, Angel Pizarro, Hakim Hammadi, Alessandro Borghi, Mariana A. Cordeiro, Fatima Zohra, A. Tülin Güleç, Ivan Ruiz Victoria, Joanna N. Łudzik, Radwa Magdy, Hisashi Uhara, Grażyna Kamińska-Winciorek, Llúcia Alòs, Pegah Kharazmi, Keisuke Suehiro, Lucian Russu, Zorica Đorđević Brlek, Sandrine Massart-Manil Massart-Manil, Moon-Bum Kim, Noha E. Hashem, Domenico Piccolo, Francesca Cicero, Jan Szymszal, Verena Ahlgrimm-Siess, Marian Gonzalez Inchaurraga, Ignazio Stanganelli, Danica Tiodorovic Zivkovic, Bugce Topukcu, Katharina Jaeger, Michael J. Inskip, Sara M. Mohy, Assya Djeridane, Véronique Del Marmol, Isil Kilinc, Nehal Yossif, Geon-Wook Kim, Oleksandr Litus, Ivana Ilić, Richard A Sturm, Mustafa Tunca, Anndressa da Matta, Elisabeth Jecel, Danijela Ćurković, Giuseppe Argenziano, Lynlee L. Lin, Elena Sotiriou, Mikela Petkovic, Suzana Kamberova, Sara Ibañes del Agua, Alan Cameron, Judit Oláh, Marc Nahuys, Leila Jeskanen, Zrinjka Paštar, Anna Wojas-Pelc, Ingela Ahnlide, Romana Čeović, Geoffrey Cains, Gilles Thuret, Mary Thomas, Marios Fragoulis, Drahomira Jarosikova, Manfred Beleut, Ferda Artüz, Brigitte Lavole, Francesco Todisco Grande, Carine Dal Pizzol, Erika Richtig, Nathalie Teixeira De Carvalho, Hans Peter Soyer, Amer M Alanazi, Vesna Sossi, Manal Bosseila, Monica Sulitan, Biancamaria Scoppio, Zrinka Bukvić Mokos, Marie-Jeanne P. Gerritsen, Mariano Suppa, Danielle Giambrone, Christoph Sinz, Jernej Kukovic, Martina Bosic, Adriana Rakowska, Eleni Mitsiou, Kely Hernandez, Ashfaq A. Marghoob, Daniel Boda, Alessandro Di Stefani, Luciana Trane, Leo Raudonikis, Akane Minagawa, Itaru Dekio, Athanassios Kyrgidis, Magdalena Wawrzynkiewicz, Katharina T Weiß, Chie Kamada, Lamberto Zara, Cristian Navarrete-Dechent, Serkan Yazici, Frédéric Renard, Leonie Mathemeier, Nissrine Amraoui, Mariana Fabris, Mariola Wyględowska-Kania, Nikolay Potekaev, Elisa Cinotti, Sedef Şahin, Peter van de Kerkhof, Silvana Ciardo, Sara Izzi, Paolo Piemonte, William V. Stoecker, Giampiero Mazzocchetti, Pasquale Frascione, Louise Lovatto, Ayşegül Yalçınkaya Iyidal, Jennifer A. Stein, Selçuk Yüksel, Daniela Ledić Drvar, Stine F. Pedersen, Dimitrios Sgouros, Meriem Bounouar, Balachandra S Ankad, Rahul Bute, Julia Brockley, Paula Aguilera-Otalvaro, Sumiko Ishizaki, Daniela Kulichova, Ilias Papadimitriou, Yeser Genc, Tanja Batinac, Jadran Bandic, Jean-Michel Lagarde, Göksun Karaman, Philipp Babilas, Mari Salmivuori, Lieven Annemans, Lennart K Blomqvist, Karel Pizinger, Duncan Lambie, Alexander Michael Witkowski, Meltem Uslu, Irena Savo, Martin Gosau, Raphaela Kastle, Olli Saksela, Pedro Zaballos, Esther De Eusebio Murillo, Hu Hui-Han, Sanda Mirela Cherciu, Claudia Artenie, Elvira Moscarella, Richard Johns, Ozlem Erdem, Valérie Vuong, Basma Birqdar, Jela Tomkova, Kasturee Jagirdar, Vassilios Lambropoulos, Moshira S. Bahrawy, Seong-Jin Kim, Su Chii Kong, Helen Schmid, Tetsuya Tsuchida, Michele Tonellato, Laura Berbegal, Lumír Pock, Iustin Hancu, Babar K Rao, Juliette Jegou, Lajos Kemény, Teresa Deinlein, Usha N. Khemani, Davive Guardoli, Juliana Arêas de Souza Lima Beltrame Ferreira, Tatiana Cristina Moraes Pinto Blumetti, Adhimukti T. Sampurna, Alexandru Telea, Ana Maria Forsea, Gionata Marazza, Lidija Kandolf Sekulovic, Marta Kurzeja, Marija Buljan, Fatima Zohra Mernissi, Alba Maiques-Diaz, Roger González, Dimitrios Kalabalikis, María Gabriela Vallone, Vanessa P. Martins Da Silva, Gemma Flores-Pons, Giuseppe Bertollo, Rolland Gyulai, Giuliana Crisman, Secil Saral, Simon Nicholson, Aimilios Lallas, Willeke Blokx, Marc A. L. M. Boone, and Oana Sindea
- Subjects
Oncology ,business.industry ,RL1-803 ,Genetics ,Medicine ,Library science ,Environmental ethics ,Dermatology ,business ,Molecular Biology - Published
- 2015
23. Intercostal leiomyoma in a child: review of the literature
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Ioannis Spyridakis, Evgenia Babatseva, Ioannis Efstratiou, Chrysostomos Kepertis, and Kleanthis Anastasiadis
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Male ,medicine.medical_specialty ,medicine.medical_treatment ,Ribs ,Case Report ,chest wall ,intercostal space ,medicine ,Humans ,Thoracotomy ,Thoracic Wall ,neoplasms ,child ,Leiomyoma ,business.industry ,Infant ,Solid mass ,General Medicine ,Leiomyoma, intercostal space, chest wall, child ,Thoracic Neoplasms ,medicine.disease ,musculoskeletal system ,female genital diseases and pregnancy complications ,Surgery ,Sixth intercostal space ,body regions ,medicine.anatomical_structure ,surgical procedures, operative ,Intercostal space ,business ,Right anterior ,Right chest ,Follow-Up Studies - Abstract
Leiomyomas of the chest wall are very rare. In a review of the current literature twelve cases were found, of which only one concerns of an intercostal leiomyoma of the chest wall. We report a case of 1 year old male child with intercostal leiomyoma who presented with a painless rigid swelling of the right chest wall. The radiological control revealed a solid mass in the right anterior sixth intercostal space. En-bloc excision of the mass by abrading of the sixth rib through right anterior thoracotomy was performed. Histopatological analysis showed a localized intercostal leiomyoma. The patient has a close follow-up for 6 months without evidence of recurrence. This is the first case of a primary intercostal leiomyoma in a child which was excised totally without reconstruction of the chest wall.
- Published
- 2017
24. The multiple faces of Langerhans cell histiocytosis in childhood: A gentle reminder
- Author
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Paraskevi Panagopoulou, Emmanuel Hatzipantelis, Maria Papadopoulou, Ioannis Efstratiou, Assimina Galli‑Tsinopoulou, Efimia Papadopoulou‑Alataki, and Anastasia Papadopoulou
- Subjects
0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,business.industry ,Cancer ,Articles ,medicine.disease ,Dermatology ,Rash ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,Langerhans cell histiocytosis ,Pathognomonic ,030220 oncology & carcinogenesis ,Diabetes insipidus ,medicine ,medicine.symptom ,Differential diagnosis ,Presentation (obstetrics) ,Bone pain ,business - Abstract
Langerhans cell histiocytosis (LCH) is a rare hematologic disorder that results from the clonal multiplication and accumulation of immature dendritic Langerhans cells. Its reported incidence rate varies, but is considered to be 2.6-8.9 per million children who are
- Published
- 2017
25. A 74-Year-Old Female with a Well Circumscribed Parietal Lobe Mass
- Author
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Alexandros Iliadis, Stella Chondromatidou, Ioannis Tsitouridis, Dimitrios Kanakis, Ioannis Efstratiou, Elsa Pazarli, and Charalampos Chrysovalantis Chytoudis-Peroudis
- Subjects
0301 basic medicine ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,business.industry ,General Neuroscience ,Parietal lobe ,Medicine ,Neurology (clinical) ,Anatomy ,business ,030217 neurology & neurosurgery ,Pathology and Forensic Medicine - Published
- 2018
26. Genetic mapping of pancreatic cancer by targeted next-generation sequencing in a cohort of patients managed with nab-paclitaxel-based chemotherapy or agents targeting the EGFR axis: a retrospective analysis of the Hellenic Cooperative Oncology Group (HeCOG)
- Author
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Iliada Bompolaki, George Glantzounis, George Pentheroudakis, Ioannis Efstratiou, Dimitra Apessou, Vassiliki Kotoula, Irene N. Nicolaou, Georgia-Angeliki Kolliou, Ioannis Tikas, Vasilios Karavasilis, Grigorios Rallis, Georgia Kafiri, George Zarkavelis, Triantafyllia Koletsa, Anna Batistatou, Kyriaki Papadopoulou, Epaminontas Samantas, George Fountzilas, Dimitrios Pectasides, and Christos Dervenis
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,EGFR ,medicine.medical_treatment ,pancreatic cancer ,Gene mutation ,medicine.disease_cause ,lcsh:RC254-282 ,Targeted therapy ,nab-paclitaxel ,CDKN2A ,Internal medicine ,Pancreatic cancer ,medicine ,Epidermal growth factor receptor ,neoplasms ,PI3K/AKT/mTOR pathway ,Original Research ,biology ,business.industry ,Retrospective cohort study ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,mutations ,medicine.disease ,biology.protein ,genetic mapping ,KRAS ,business - Abstract
Pancreatic cancer is one of the most fatal malignancies ranking fourth among the leading causes of cancer death with diagnosis at late stages carrying a dismal prognosis. The aim of our retrospective study was to describe the nature and the incidence of gene mutations and genomic instability in advanced pancreatic adenocarcinomas of a Greek patient population fully annotated with clinicopathological data. We used a targeted next-generation sequencing (NGS) panel encompassing genes commonly mutated in pancreatic tumours in a patient population managed with either nab-paclitaxel regimens or targeted compounds modulating the epidermal growth factor receptor (EGFR)/AKT/mTOR axis. We identified KRAS, TP53, SMAD4 and CDKN2A as being the most prevalent mutations in the study population with the exception of an intriguingly lower incidence regarding KRAS mutants. Homologous recombination gene mutations were found to be mutually exclusive with CDKN2A mutations. The coexistence of both KRAS and TP53 mutation seems to adversely affect the outcome of the patients whether treated with targeted therapy against EGFR/Akt/mTOR axis or cytotoxic drugs. The poor prognosis observed, correlated to late presentation, specific molecular mutations and to high mutational load warrant prospective validating studies and research into the mechanistic pathophysiology of pancreatic tumours for more effective therapeutic targeting.
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- 2019
27. Sclerotic Regressing Large Congenital Nevus
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Vasilios Lambropoulos M.D., Ioannis Efstratiou, Dimitrios Sotiriadis, Olga Pikou, Miltiadis Kokolios, and Aikaterini Patsatsi
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medicine.medical_specialty ,Pathology ,Nevus, Pigmented ,Sclerosis ,integumentary system ,business.industry ,Dermatology ,medicine.disease ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Hair loss ,In utero ,Congenital melanocytic nevus ,030220 oncology & carcinogenesis ,Pediatrics, Perinatology and Child Health ,Rare case ,Congenital nevus ,medicine ,Humans ,Female ,skin and connective tissue diseases ,business ,Child - Abstract
Regression of congenital nevi is usually associated with loss of pigment or halo formation. In rare cases, regression is characterized by sclerosis and hair loss. We describe a rare case of a sclerotic hypopigmented large congenital melanocytic nevus in which a localized scleroderma-like reaction process of regression seemed to have started in utero and progressed throughout early childhood.
- Published
- 2016
28. Tumor Infiltrating Lymphocytes Affect the Outcome of Patients with Operable Triple-Negative Breast Cancer in Combination with Mutated Amino Acid Classes
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Paris Kosmidis, Amanda Psyrri, Irene Nicolaou, Gerasimos Aravantinos, Flora Zagouri, George Pentheroudakis, Zoi Alexopoulou, Sotiris Lakis, Christos Papadimitriou, Evangelia Razis, Ioannis Efstratiou, George Fountzilas, Vassiliki Kotoula, Eleni Giannoulatou, Ioannis S. Vlachos, Dimitrios Pectasides, Kyriakos Chatzopoulos, Kyriaki Papadopoulou, Pavlos Papakostas, Maria Sotiropoulou, and Helen Gogas
- Subjects
0301 basic medicine ,Cancer Treatment ,lcsh:Medicine ,medicine.disease_cause ,0302 clinical medicine ,Breast Tumors ,Basic Cancer Research ,Medicine and Health Sciences ,Medicine ,Stromal tumor ,lcsh:Science ,Immune Response ,Triple-negative breast cancer ,Mutation ,Multidisciplinary ,hemic and immune systems ,Nonsense Mutation ,Genomics ,Phenotype ,Oncology ,030220 oncology & carcinogenesis ,Amino Acid Analysis ,Anatomy ,Research Article ,Histology ,Concordance ,Nonsense mutation ,Immunology ,chemical and pharmacologic phenomena ,Research and Analysis Methods ,03 medical and health sciences ,Breast cancer ,Cancer Genomics ,Genomic Medicine ,Breast Cancer ,Genetics ,Molecular Biology Techniques ,Molecular Biology ,Molecular Biology Assays and Analysis Techniques ,business.industry ,Tumor-infiltrating lymphocytes ,lcsh:R ,Biology and Life Sciences ,Cancers and Neoplasms ,medicine.disease ,030104 developmental biology ,Cancer research ,lcsh:Q ,business - Abstract
Background Stromal tumor infiltrating lymphocytes (TILs) density is an outcome predictor in triple-negative breast cancer (TNBC). Herein we asked whether TILs are related to coding mutation load and to the chemical class of the resulting mutated amino acids, i.e., charged, polar, and hydrophobic mutations. Methods We examined paraffin tumors from TNBC patients who had been treated with adjuvant chemotherapy mostly within clinical trials (training cohort, N = 133; validation, N = 190) for phenotype concordance; TILs density; mutation load and types. Results Concordance of TNBC phenotypes was 42.1% upon local / central, and 72% upon central / central pathology assessment. TILs were not associated with mutation load, type and class of mutated amino acids. Polar and charged mutation patterns differed between TP53 and PIK3CA (p50% TILs tumors (training p = 0.003; validation p = 0.015). Conclusions TILs density is unrelated to mutation load in TNBC, which may be regarded as an unstable phenotype. If further validated, hydrophobic mutations along with TILs density may help identifying TNBC patients in higher risk for relapse.
- Published
- 2016
29. Value of Magnetic Resonance Imaging in Diagnosis of Adenomyosis and Myomas of the Uterus
- Author
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Basil C. Tarlatzis, Athanasios Dimitriadis, Charalampos P. Stamatopoulos, P. Stamatopoulos, Grigoris F. Grimbizis, Themistoklis Mikos, and Ioannis Efstratiou
- Subjects
Adult ,medicine.medical_specialty ,medicine.medical_treatment ,Hysterectomy ,Sensitivity and Specificity ,Cohort Studies ,Obstetrics and gynaecology ,Predictive Value of Tests ,Humans ,Medicine ,Single-Blind Method ,Adenomyosis ,Prospective Studies ,Prospective cohort study ,Leiomyoma ,Uterine sarcoma ,medicine.diagnostic_test ,business.industry ,Obstetrics and Gynecology ,Magnetic resonance imaging ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,ROC Curve ,Predictive value of tests ,Uterine Neoplasms ,Female ,Enlarged Uterus ,Radiology ,business - Abstract
Study Objective: To estimate the diagnostic performance of magnetic resonance imaging (MRI) in detection of myomas and adenomyosis of the uterus. Design: Prospective cohort observational study (Canadian Task Force classification II-2). Setting: Department of obstetrics and gynecology, tertiary academic hospital. Patients: One hundredfifty-three consecutivewomen with an enlarged uterus accompanied by gynecologic symptoms and/or with an asymptomatic pelvic mass. Intervention: Total abdominal hysterectomy. All patients underwent MRI before the operation. Measurements and Main Results: The sensitivity, specificity, positive, and negative predictive value of MRI for the diag- nosis of uterine pathology was calculated using histologic findings as the standard criterion for final diagnosis. Receiver op- erating characteristics curves were constructed to describe the diagnostic performance of MRI. In the diagnosis of myomas, MRI demonstrated sensitivity of 94.1%, specificity of 68.7%, PPVof 95.7%, and NPVof 61.1%. In the diagnosis of adeno- myosis, MRI demonstrated sensitivity of 46.1%, specificity of 99.1%, PPVof 92.3%, and NPVof 88.5%. The area under the curve (AUC) for the diagnostic performance of MRI in the detection of myomas and adenomyosis was 0.81 and 0.73, respec- tively. Uterine sarcoma was diagnosed in 5 patients; in these cases, MRI demonstrated sensitivity of 60.0%, specificity of 99.2%, PPVof 75.0%, and NPVof 98.4%. The AUC for MRI in the diagnosis of uterine sarcomas was 0.80. Conclusions: MRI exhibits a high AUC for the diagnosis of both adenomyosis and myomas. The PPVof MRI in the diagnosis of adenomyosis and myomas of the uterus is high as well. MRI seems to be a useful technique in everyday clinical practice in the diagnostic approach of these common conditions, enabling clinicians to select the most appropriate management. Journal of Minimally Invasive Gynecology (2012) 19, 620-626 2012 AAGL. All rights reserved.
- Published
- 2012
30. Intrinsic tumor features underlying clinical subtype discordance in early breast cancer
- Author
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Helen Gogas, K. Manousou, Vasiliki Kotoula, Ioannis Tikas, Sotiris Lakis, Angelos Koutras, Georgios Pentheroudakis, G. Fountzilas, Dimitris Bafaloukos, D.G. Pectasides, Flora Zagouri, Christos N. Papandreou, Kyriaki Papadopoulou, Eleni Giannoulatou, Ioannis Efstratiou, Mattheos Bobos, A. Psyrri, Pavlos Papakostas, C. Christodoulou, and Georgios Lazaridis
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,Medicine ,Hematology ,business ,Early breast cancer - Published
- 2017
31. Evaluation of the association of PIK3CA mutations and PTEN loss with efficacy of trastuzumab therapy in metastatic breast cancer
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Kalliopi Petraki, Konstantine T. Kalogeras, Dimitrios Pectasides, George Rigakos, Kitty Pavlakis, George Fountzilas, D.V. Skarlos, Vassiliki Kotoula, Dimitris Bafaloukos, Anastasia G Eleftheraki, Ioannis Efstratiou, E. Razis, Haralabos P. Kalofonos, Mattheos Bobos, Pavlos Papakostas, Ioannis Kostopoulos, Gerassimos Aravantinos, First Department of Medical Oncology, 'Hygeia' Hospital, Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki School of Medicine, Department of Pathology, Section of Biostatistics, Hellenic Cooperative Oncology Group, Division of Oncology, Department of Medicine, University Hospital of Patras, Obstetrical and Gynaecological Center 'Iasso', Department of Oncology, 'Hippokration' Hospital, Third Department of Medical Oncology, 'Agii Anargiri' Cancer Hospital, School of medicine [Thessaloniki], Aristotle University of Thessaloniki-Aristotle University of Thessaloniki, 'Metropolitan' Hospital, Oncology Section, Second Propaedeutic Department of Internal Medicine, University General Hospital 'Attikon', Department of Medical Oncology, Translational Research Section, and Second Department of Medical Oncology
- Subjects
PTEN ,Cancer Research ,Lung Neoplasms ,Time Factors ,Receptor, ErbB-2 ,Predictive ,Polymerase Chain Reaction ,Immunoenzyme Techniques ,Phosphatidylinositol 3-Kinases ,Breast cancer ,Trastuzumab ,skin and connective tissue diseases ,In Situ Hybridization, Fluorescence ,Aged, 80 and over ,education.field_of_study ,biology ,Liver Neoplasms ,Antibodies, Monoclonal ,DNA, Neoplasm ,Middle Aged ,Survival Rate ,Treatment Outcome ,Receptors, Estrogen ,Oncology ,Lymphatic Metastasis ,Disease Progression ,Female ,Breast disease ,Receptors, Progesterone ,medicine.drug ,Adult ,Class I Phosphatidylinositol 3-Kinases ,Population ,Antineoplastic Agents ,Bone Neoplasms ,Breast Neoplasms ,Antibodies, Monoclonal, Humanized ,Polymorphism, Single Nucleotide ,HER2 ,medicine ,Humans ,education ,neoplasms ,Survival rate ,PI3K/AKT/mTOR pathway ,Aged ,Retrospective Studies ,PTEN Phosphohydrolase ,Cancer ,PIK3CA ,medicine.disease ,Tissue Array Analysis ,Mutation ,Cancer research ,biology.protein ,Proto-Oncogene Proteins c-akt ,Follow-Up Studies - Abstract
International audience; Trastuzumab (T) is effective in metastatic breast cancer (MBC) with HER2 overexpression and/or amplification, but resistance to T develops in a significant number of HER2-positive patients. Understanding the mechanisms of resistance is critical to the care of these patients. Formalin-fixed paraffin-embedded tumor tissue samples were collected from 256 patients with T-treated MBC. Clinical information was collected retrospectively from the patients' medical records. Central review of HER2 status by fluorescent in situ hybridization (FISH) and/or immunohistochemistry (IHC) revealed that of the 227 eligible patients only 139 (61%) were truly HER2-positive. PTEN, ER, PgR, and Ki67 were evaluated by IHC, while PTEN status was evaluated by FISH as well. PIK3CA mutations were identified with single nucleotide polymorphism (SNP) genotyping. Median time to progression (TTP) was 14.4 months for the HER2-positive and 10.3 for the HER2-negative patients (log-rank, = 0.22). Survival from the initiation of T (survivalT) was 50.4 months for the HER2-positive and 35.3 for the HER2-negative subgroups ( = 0.006). Higher risk of progression was associated with HER2-positive status and the presence of PIK3CA mutations ( = 0.014). PTEN loss, as determined by IHC, was associated with lower survivalT in the whole population ( = 0.029) and in the HER2-positive population ( = 0.017). PIK3CA mutations and/or PTEN loss status were evaluated together as a single parameter, to estimate the impact of activation of the PI3K/AKT molecular pathway, and it was significantly associated with both decreased TTP ( = 0.003 in the total population, = 0.004 in HER2-positive patients) and survival (survivalT, = 0.011 in total, = 0.006 in HER2-positive). In this trastuzumab-treated breast cancer population, PIK3CA activating mutations were associated with shorter TTP and PTEN loss with decreased survival. The activation of the PI3K/AKT pathway from either defect was associated with both TTP and survival, indicating the adverse effect of this pathway's status on trastuzumab efficacy.
- Published
- 2011
32. Predictive significance of tumour angiogenic and anti-angiogenic VEGF-A splice variants in patients with metastatic colorectal cancer
- Author
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Georgia-Angeliki Koliou, D.G. Pectasides, Ioannis Efstratiou, Pavlos Papakostas, Iliada Bompolaki, G. Papatsibas, Georgios Oikonomopoulos, Georgios Pentheroudakis, Epaminontas Samantas, G. Fountzilas, Dimitris Bafaloukos, Thomas Makatsoris, Georgios Zarkavelis, Davide Mauri, A. Psyrri, Kyriaki Papadopoulou, Anna Goussia, Vasiliki Kotoula, Vasilios Karavasilis, and A. Christopoulou
- Subjects
biology ,Colorectal cancer ,business.industry ,VEGF receptors ,Anti angiogenic ,Hematology ,medicine.disease ,Oncology ,biology.protein ,medicine ,Cancer research ,In patient ,splice ,business - Published
- 2018
33. P3.01-61 EGFR and KRAS Mutational Status and Significance in Greek Patients with Advanced Non Small Cell Lung Cancer
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E Res, Vasilios Karavasilis, Vasiliki Kotoula, Giannis Mountzios, Thomas Zaramboukas, Ioannis Efstratiou, Emily Daskalaki, D. Televantou, Paris Kosmidis, Kostas N. Syrigos, Dimitrios G. Pectasides, X. Mavropoulou, Kyriaki Papadopoulou, George Kouvatseas, Helena Linardou, A. Kalogera-Fountzila, Grigorios Rallis, George Fountzilas, Epaminontas Samantas, and Sofia Lambaki
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,business.industry ,Cancer research ,Mutational status ,Medicine ,KRAS ,Non small cell ,business ,medicine.disease_cause ,Lung cancer ,medicine.disease - Published
- 2018
34. Clinical relevance of primary tumor site and respective molecular characteristics in patients with early-stage colorectal cancer
- Author
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Christos Christodoulou, Ioannis Tikas, Kyriaki Manousou, Kyriaki Papadopoulou, George K. Koukoulis, George Fountzilas, Kleo Papaparaskeva, Sofia Chrisafi, Georgios K. Glantzounis, Amanda Psyrri, Vassiliki Kotoula, Ioannis Efstratiou, Dimitrios G. Pectasides, Vasilios Karavasilis, Christos Poulios, Elena Fountzilas, George Papatsibas, George Pentheroudakis, Ioannis Varthalitis, and Gerasimos Aravantinos
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Colorectal cancer ,business.industry ,medicine.disease ,Primary tumor ,Internal medicine ,medicine ,Clinical significance ,In patient ,Stage (cooking) ,business - Abstract
e15606Background: Right- and left-sided colorectal cancers (CRC) demonstrate a distinct clinical behavior. Whether this heterogeneity is associated with specific molecular profiles has yet to be de...
- Published
- 2018
35. PAI-1 and HER2 interaction in advanced breast cancer disease: evidence for added benefit from trastuzumab in HER2-negative patients
- Author
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Dimosthenis Miliaras, Maria Sotiropoulou, Dimitrios Bafaloukos, Ioannis Efstratiou, Pavlos Papakostas, Georgia Karayannopoulou, Georgia Gourgioti, Anna Batistatou, Anna Koumarianou, Konstantine T. Kalogeras, George Pentheroudakis, Gerasimos Aravantinos, Evangelia Razis, Eleni Galani, Mattheos Bobos, Dimitrios Pectasides, George Fountzilas, Kalliopi Petraki, and Haralabos P. Kalofonos
- Subjects
Oncology ,Adult ,Cancer Research ,medicine.medical_specialty ,Receptor, ErbB-2 ,medicine.medical_treatment ,Breast Neoplasms ,Toxicology ,Lower risk ,Antibodies, Monoclonal, Humanized ,chemistry.chemical_compound ,Breast cancer ,Trastuzumab ,Internal medicine ,Plasminogen Activator Inhibitor 1 ,medicine ,Humans ,Pharmacology (medical) ,skin and connective tissue diseases ,neoplasms ,Aged ,Retrospective Studies ,Pharmacology ,Aged, 80 and over ,Chemotherapy ,Proportional hazards model ,business.industry ,Cancer ,Retrospective cohort study ,Middle Aged ,medicine.disease ,chemistry ,Plasminogen activator inhibitor-1 ,Female ,business ,medicine.drug - Abstract
The urokinase plasminogen activator (uPA) and the plasminogen activator inhibitor 1 (PAI-1) are associated with an aggressive course in breast cancer and are used to determine whether chemotherapy is needed in node-negative patients. The objective of the study was to evaluate the prognostic value of uPA and PAI-1 protein expression in advanced breast cancer patients treated with trastuzumab. Formalin-fixed paraffin-embedded tumor tissue samples were retrospectively collected from 230 patients with advanced breast cancer treated with trastuzumab and 130 patients treated with 1st line taxanes. uPA, PAI-1, ER, PgR, HER2 and Ki67 protein expression was evaluated by immunohistochemistry. Central review of HER2 status revealed that only 144 (63 %) of the trastuzumab-treated patients were truly HER2-positive. Median survival was 50.7 months for the HER2-positive and 30.1 months for the HER2-negative patients (p = 0.006) treated with trastuzumab. In multivariate Cox regression analysis of the trastuzumab cohort, a significant interaction was found, in terms of survival, between HER2 status and PAI-1 protein expression in the stroma (Wald’s p = 0.002). Positive PAI-1 protein expression in the stroma of HER2-negative patients was associated with lower risk of death (HR 0.35, 95 % CI 0.19–0.65, Wald’s p = 0.0008). Such an association was not observed in HER2-positive patients treated with trastuzumab or in the non-trastuzumab (validation) cohorts. Our results suggest that positive stromal PAI-1 protein expression may identify a subgroup of HER2-negative advanced breast cancer patients who might benefit from treatment with trastuzumab. Further studies are warranted to validate these findings in larger cohorts.
- Published
- 2015
36. Adjuvant Dose-Dense Sequential Chemotherapy with Epirubicin, CMF, and Weekly Docetaxel Is Feasible and Safe in Patients with Operable Breast Cancer
- Author
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Eleni Timotheadou, Ioannis Efstratiou, Christos Christodoulou, Theofanis Economopoulos, George Fountzilas, Pavlos Papakostas, Dimitrios G. Pectasides, Dimosthenis Skarlos, Helen Gogas, and Christos Papadimitriou
- Subjects
Adult ,Oncology ,Cancer Research ,medicine.medical_specialty ,Anthracycline ,Cyclophosphamide ,medicine.medical_treatment ,Breast Neoplasms ,Docetaxel ,Breast cancer ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Aged ,Epirubicin ,Chemotherapy ,Dose-Response Relationship, Drug ,business.industry ,Hematology ,General Medicine ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Regimen ,Methotrexate ,Chemotherapy, Adjuvant ,Feasibility Studies ,Female ,Taxoids ,Fluorouracil ,business ,Febrile neutropenia ,medicine.drug - Abstract
Currently, randomized phase III trials have demonstrated that docetaxel is an effective strategy in the adjuvant treatment of breast cancer. However, previous attempts to incorporate docetaxel with an anthracycline in a dose-dense regimen have been unsuccessful. Therefore, new schedules containing both drugs should be explored. Forty-four patients with high-risk operable breast cancer entered this feasibility study. They were treated with three cycles of epirubicin 110 mg/m2 every 2 wk with G-CSF followed by three cycles of "intensified" CMF (840 mg/m2 cyclophosphamide; 57 mg/m2 methotrexate; 840 mg/m2 fluorouracil) every 2 wk with G-CSF followed 3 wk later by nine weekly cycles of 35 mg/m2 docetaxel (E-CMF-doc). Totally, 39 patients (89%) received all cycles of chemotherapy. The vast majority (92%) of cycles were administered at full dose. Therefore, dose intensity was sufficiently maintained for all drugs. Toxicity was generally mild to moderate. Most frequently recorded side effects apart from alopecia were neutropenia (54%) and nausea/vomiting (89%). Infection developed in nine patients. Two cases of febrile neutropenia were reported. The E-CMF-doc regimen, as used in this study, is feasible and well tolerated. Its impact on survival should be evaluated in phase III trials.
- Published
- 2006
37. Primary Malignant Fibrous Histiocytoma of the Jejunum Metastatic to the Spine: Report of a Case
- Author
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Ioannis Efstratiou, Constantine P. Spanos, Dimitrios Kiskinis, Stamatia Aggelidou, Sotiris Trigonis, and Theodoros Syrrakos
- Subjects
Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Computed tomography ,Partial small bowel obstruction ,Resection ,Metastasis ,Jejunum ,Lesion ,Endocrinology ,Intussusception (medical disorder) ,medicine ,Humans ,Spinal Neoplasms ,Histiocytoma, Benign Fibrous ,Jejunal Neoplasms ,medicine.diagnostic_test ,business.industry ,Gastroenterology ,medicine.disease ,Surgery ,Radiation therapy ,medicine.anatomical_structure ,Oncology ,medicine.symptom ,Tomography, X-Ray Computed ,business ,Intussusception - Abstract
We report a case of malignant fibrous histiocytoma (MFH) metastatic to the spine. A 41-yr-old male was admitted to our hospital for radiation treatment of MFH of the spine. He began to show signs suggestive of partial small bowel obstruction. Computed tomography demonstrated jejuno-jejunal intussusception. The patient was taken to the operating room, where the diagnosis was confirmed. Partial jejunal resection was performed. The lead point of the intussusception was histologically diagnosed to be a high-grade malignant fibrous histiocytoma. We believe that the spinal lesion was the metastatic lesion and that metastasis occurred via the vessels of Adamciewicz. To our knowledge this is the first case thus reported.
- Published
- 2005
38. Value of the Cervical Compartments in the Surgical Treatment of Papillary Thyroid Carcinoma
- Author
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Andreas Christodoulou, Ioannis Efstratiou, Asterios Samaras, Persefoni Xirou, Theodoros Ntitsias, Konstantinos Karamoshos, Apostolos Goropoulos, and Konstantinos Paulou
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Adolescent ,Lymphovascular invasion ,Biopsy, Fine-Needle ,Metastasis ,Thyroid carcinoma ,Modified Radical Neck Dissection ,Biopsy ,medicine ,Carcinoma ,Humans ,Thyroid Neoplasms ,Lymph node ,Aged ,medicine.diagnostic_test ,business.industry ,Thyroid ,Middle Aged ,medicine.disease ,Carcinoma, Papillary ,medicine.anatomical_structure ,Lymphatic Metastasis ,Thyroidectomy ,Neck Dissection ,Female ,Surgery ,Lymph Nodes ,business ,Algorithms - Abstract
In the treatment of papillary thyroid carcinoma (PTC), supplementary lymph node dissection (LND) is not well standardized. The purpose of this study was to evaluate the significance of the cervical compartments in the lymphatic spread of PTC and the impact of modified radical neck dissection (MRND) as an additional surgical procedure to thyroid resection. From 1999 to 2002, LND of the central compartment (compartment A) was performed in 39 patients. Among this group, additional MRND of the ipsilateral compartment (compartment B) and the contralateral compartment (compartment C) was performed in 29 and 15 patients respectively, who met the selection criteria. The mean number of nodes resected was 11 (5-22) in compartment A, 23 (8-37) in compartment B, and 22 (10-31) in compartment C. Histopathologic findings revealed node invasion of compartment A in 25 patients (64.1%), of A and B in 20 patients (51,2%) and of A, B, and C in 13 patients (33.3%). From the 25 patients with metastases in compartment A, 80% (20 patients) already had metastases in compartment B and 52% (13 patients) had metastases in all three compartments. All patients free of metastasis (M0) in compartment A were also metastasis free in both lateral compartments. Postoperative whole-body scanning I(131) in M0 patients showed no uptake at all. Mapping of the cervical anatomy in compartments seems to be a useful taxonomy for clarifying the lymphatic spread of PTC. Patients having PTC without metastasis in compartment A are almost certainly disease free at the time of operation. Lymph node metastasis in the central compartment appears to be a valuable indicator of lymphatic invasion of the lateral compartment and a strong indication for performance of a unilateral or bilateral MRND to complete the surgical removal of tumor.
- Published
- 2004
39. AMALTHEA: A prospective, single-arm study of the Hellenic Cooperative Oncology Group evaluating the efficacy and safety of 1st line FOLFIRI+Aflibercept in patients with metastatic colorectal cancer
- Author
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Georgios Pentheroudakis, Ioannis Efstratiou, Dimitris Bafaloukos, G Koumakis, C Petraki, Ioannis Souglakos, Emily Daskalaki, G. Fountzilas, D.G. Pectasides, Epaminontas Samantas, Eleni Vrettou, Georgia-Angeliki Koliou, Vasiliki Kotoula, Ioannis Tikas, Vasilios Karavasilis, Christos Poulios, and Gerassimos Aravantinos
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,Colorectal cancer ,Hematology ,medicine.disease ,Internal medicine ,FOLFIRI ,Medicine ,In patient ,business ,Single Arm Study ,Aflibercept ,medicine.drug - Published
- 2017
40. Intact or broken-apart RNA: an alternative concept for ALK fusion screening in non-small cell lung cancer (NSCLC)
- Author
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George Fountzilas, Larisa V. Debelenko, Sofia Chrisafi, Vassiliki Kotoula, Eleftheria Tsolaki, Amanda Psyrri, Kyriaki Papadopoulou, Paris Kosmidis, Catherine Michail-Strantzia, Maria Vassilakopoulou, George Lazaridis, Ioannis Efstratiou, and Mattheos Bobos
- Subjects
Oncology ,Male ,medicine.medical_specialty ,Histology ,Lung Neoplasms ,Oncogene Proteins, Fusion ,Pyridines ,non-small cell lung cancer (NSCLC) ,Antineoplastic Agents ,In situ hybridization ,Biology ,Translocation, Genetic ,Pathology and Forensic Medicine ,Crizotinib ,Predictive Value of Tests ,hemic and lymphatic diseases ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,medicine ,Anaplastic lymphoma kinase ,Humans ,Anaplastic Lymphoma Kinase ,RNA, Messenger ,Diagnostic Errors ,Survival analysis ,In Situ Hybridization, Fluorescence ,Aged ,Neoplasm Staging ,Messenger RNA ,RNA ,Receptor Protein-Tyrosine Kinases ,Middle Aged ,medicine.disease ,Prognosis ,Immunohistochemistry ,Survival Analysis ,Medical Laboratory Technology ,Cancer research ,Pyrazoles ,Female ,medicine.drug - Abstract
Anaplastic lymphoma kinase (ALK) break-apart fluorescent in situ hybridization (FISH) is currently used in diagnostics for the selection of non-small cell lung cancer (NSCLC) patients to receive crizotinib. We evaluated ALK status in NSCLC with a novel ALK mRNA test based on the break-apart FISH concept, which we called break-apart transcript (BAT) test. ALK5' and ALK3' transcript patterns were established with qPCR for ALK-expressing controls including fusion-negative neuroblastomas, as well as fusion-positive anaplastic large cell lymphomas and NSCLC. The BAT test was evaluated on 271 RNA samples from routinely processed paraffin NSCLC tissues. Test results were compared with ALK FISH (n=121), immunohistochemical (IHC) analysis (n=86), and automated quantitative analysis (AQUA, n=83). On the basis of the nonoverlapping ALK BAT patterns in ALK-expressing controls (P0.0001), 8/174 adenocarcinomas (4.6%) among 259 informative NSCLC were predicted as fusion positive. Overall concordance for paired method results was high (94.1% to 98.8%) but mainly concerned negative prediction because of the limited availability of positive-matched cases. Tumors with 100% cytoplasmic IHC staining of any intensity (n=3) were positive for AQUA, FISH, and BAT test; tumors with lower IHC positivity and different staining patterns were AQUA-negative. Upon multiple reevaluations, ALK gene status was considered as originally misinterpreted by FISH in 3/121 cases (2.5%). Tumors with4 ALK gene copies were associated with longer overall survival upon first-line chemotherapy. In conclusion, application of the ALK BAT test on routinely processed NSCLC tissues yields the same fusion partner independent information as ALK break-apart FISH but is more robust and cost-effective. The BAT concept may be considered for the development of further drug-predictive translocation tests.
- Published
- 2014
41. Prognostic and predictive value of p-Akt, EGFR, and p-mTOR in early breast cancer
- Author
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Anastasia G Eleftheraki, Georgios Lazaridis, Irene Papaspirou, Georgia Karayannopoulou, George Fountzilas, George Pentheroudakis, Sofia Lambaki, Ioannis Efstratiou, Mattheos Bobos, and Nikolaos Zamboglou
- Subjects
Oncology ,medicine.medical_specialty ,Low protein ,medicine.medical_treatment ,Breast Neoplasms ,Risk Assessment ,Sensitivity and Specificity ,Breast cancer ,Internal medicine ,Biomarkers, Tumor ,Medicine ,PTEN ,Humans ,Radiology, Nuclear Medicine and imaging ,Survival rate ,Early Detection of Cancer ,Univariate analysis ,biology ,Greece ,business.industry ,Incidence ,TOR Serine-Threonine Kinases ,Reproducibility of Results ,medicine.disease ,Prognosis ,Radiation therapy ,ErbB Receptors ,Oncogene Protein v-akt ,Survival Rate ,biology.protein ,Hormonal therapy ,Immunohistochemistry ,Female ,business - Abstract
There are scarce data available on the prognostic/predictive value of p-Akt and p-mTOR protein expression in patients with high-risk early breast cancer. Formalin-fixed paraffin-embedded (FFPE) tumor tissue samples from 997 patients participating in two adjuvant phase III trials were assessed for EGFR, PTEN, p-Akt, p-mTOR protein expression, and PIK3CA mutational status. These markers were evaluated for associations with each other and with selected patient and tumor characteristics, immunohistochemical subtypes, disease-free survival (DFS), and overall survival (OS). p-mTOR protein expression was negatively associated with EGFR and positively associated with PTEN, with p-Akt473, and with the presence of PIK3CA mutations. EGFR expression was positively associated with p-Akt473, p-Akt308, and PIK3CA wild-type tumors. Finally, p-Akt308 was positively associated with p-Akt473 expression. In univariate analysis, EGFR (p = 0.016) and the coexpression of EGFR and p-mTOR (p = 0.015) were associated with poor OS. Among patients with p-Akt308-negative or low-expressing tumors, those treated with hormonal therapy were associated with decreased risk for both relapse and death (p = 0.013 and p
- Published
- 2014
42. Hemorrhagic bullae and skin fragility â a clinicopathologic challenge
- Author
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Myrto Trakatelli, Dimitrios Sotiriadis, Ioannis Efstratiou, Dimitrios Kalabalikis, and Aikaterini Patsatsi
- Subjects
medicine.medical_specialty ,Pathology ,medicine.diagnostic_test ,business.industry ,Amyloidosis ,MEDLINE ,Dermatology ,medicine.disease ,Hemorrhagic disorder ,Skin fragility ,Biopsy ,medicine ,business - Published
- 2010
43. Reconstruction of skin avulsion injuries of the upper extremity with integra(®) dermal regeneration template and skin grafts in a single-stage procedure
- Author
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Alexandros Dionyssopoulos, Ioannis Efstratiou, Katerina Kaidoglou, Efterpi Demiri, Dimitrios Dionyssiou, and Antonios Papaconstantinou
- Subjects
Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Dermatologic Surgical Procedures ,Artificial skin ,Grip strength ,Forearm ,Skin Physiological Phenomena ,Medicine ,Humans ,Regeneration ,Orthopedics and Sports Medicine ,Retrospective Studies ,Skin ,Skin, Artificial ,Arm Injuries ,Debridement ,integumentary system ,business.industry ,Regeneration (biology) ,Chondroitin Sulfates ,General Medicine ,Skin Transplantation ,Middle Aged ,Plastic Surgery Procedures ,Skin Avulsion Injuries ,Surgery ,medicine.anatomical_structure ,Orthopedic surgery ,Female ,Collagen ,business - Abstract
Management of skin avulsion injuries of the upper extremity may require coverage with large flaps or skin autografts. Cutaneous grafting is frequently combined with artificial skin to optimize the final functional and cosmetic result. The conventional use of bilaminated dermal substitutes consists of a two-stage procedure and requires long immobilization of the operated area. The purpose of this retrospective study is to evaluate the impact of a dermal regeneration template immediately covered by skin grafts in a one-step procedure for reconstructing skin avulsion injuries of the hand and forearm.We performed this technique in eight patients who presented with extended skin defects of the hand and forearm following skin avulsion injuries. Dimensions of the defects ranged from 160 to 1,250 cm(2). After debridement, Integra(®) Single Layer was applied and covered with unmeshed thin skin autografts; compressive dressings were used for 1 week and mobilization started by the second postoperative week. Histological examination of the grafted areas was performed 2 weeks after surgery. Functional and cosmetic outcome was assessed 12 months postoperatively.The overall take rate of the dermal substitute and skin graft was 95-98 %. Histological results showed complete incorporation and vascular proliferation of the template, which allowed the neo-vascularization of the overlying autograft. The mean grip strength of the operated hands was at the 83 % of the normal contralateral hands. Pliability and overall appearance of the reconstructed areas was satisfactory (mean Vancouver Scar Scale Score 1.875).The use of Integra(®) Single Layer dermal substitute and immediate skin overgrafting consists an alternative reconstructive option for managing extended skin avulsion injuries of the upper extremity; it reduces postoperative immobilization, minimizes donor site morbidity and provides good functional and esthetic results in a single surgical procedure.
- Published
- 2013
44. Impact of genomic heterogeneity and mutation patterns on the outcome of patients with epithelial ovarian cancer (EOC)
- Author
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G. Fountzilas, Sotiris Lakis, Ioannis Efstratiou, Sofia Chrisafi, Vasiliki Kotoula, Alexios Papanikolaou, Ioannis Tikas, Florentia Fostira, Georgios Lazaridis, Elpida Charalambous, George Kouvatseas, Basil C. Tarlatzis, and Eleni Giannoulatou
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,Mutation (genetic algorithm) ,Medicine ,Epithelial ovarian cancer ,Hematology ,business - Published
- 2016
45. Abstract 538: A role for mutated hydrophobic amino acids in patients with triple-negative breast cancer
- Author
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Zoi Alexopoulou, George Fountzilas, Maria Sotiropoulou, Helen Gogas, Spyros Miliaras, Flora Zagouri, Ioannis S. Vlachos, George Pentheroudakis, Ioannis Efstratiou, Sotiris Lakis, Eleni Timotheadou, Kyriaki Papadopoulou, Vassiliki Kotoula, Eleni Giannoulatou, George C. Zografos, and Dimitrios Pectasides
- Subjects
Oncology ,chemistry.chemical_classification ,Cancer Research ,medicine.medical_specialty ,chemistry ,business.industry ,Internal medicine ,medicine ,In patient ,business ,Triple-negative breast cancer ,Amino acid - Abstract
Background - Aim: Nodal status and stromal tumor infiltrating lymphocyte (TILs) density are independently associated with patient outcome in triple-negative breast cancer (TNBC). Herein we examined whether the nature of tumoral mutated amino acids, in association with TILs and nodal status, interferes with the outcome of patients with operable TNBC treated with adjuvant chemotherapy.Methods: Two independent cohorts of TNBC patients and tumors were examined: (a) 133 patients treated upon clinical service (training set; TS), and (b) 190 patients treated in the context of phase III adjuvant trials (validation set; VS). All 323 patients had received adjuvant anthracycline-taxanes chemotherapy. All 323 tumors yielded informative data upon massively parallel sequencing for breast cancer related targets in 47 genes. Amino acid changing variants were considered as mutations (MUT) for minor allele frequencies 50% TILs) and nonLP. Disease-free survival (DFS) was the clinical endpoint.Results: The 2 cohorts did not differ regarding MUT tumor incidence (TS, 71%; VS, 67%); TILs (10% LP in each set); nodal status (TS, 0-3 positive nodes in 68%; VS, 64%); and, MUT a.a. classes (TS, charged 11%, polar 25%, hydrophobic 13%, mixed 15%; VS, 12%, 17%, 9%, and 13%, respectively). No statistically significant difference was obtained in the rates of MUT tumors or MUT a.a. classes with respect to TILs and nodal status. In the TS, patients with tumors bearing hydrophobic MUT a.a. fared worse than those with other MUT types (HR 2.43, 95%CI 1.17-5.03, p = 0.017) or than those without MUT (HR 5.13, 95%CI 1.95-13.52, p3 positive nodes and non-LP tumors (TS, HR 3.03, 95%CI 1.11-8.29, p = 0.031; VS, HR 2.90, 95%CI 0.97-8.70, p = 0.057). Patients with >3 positive nodes, non-LP tumors with hydrophobic MUT a.a. were revealed as the only subset with significantly worse DFS when compared to patients with LP tumors in both TS (p = 0.003) and VS (p = 0.015). Charged and polar MUT a.a., as well as the presence of MUT in the most frequently affected genes (TP53 and PIK3CA) did not have any impact on DFS in either TS or VS.Conclusions: In the adjuvant setting, the presence of hydrophobic MUT a.a. seems to be associated with worst prognosis in nonLP TNBC patients with high nodal burden. The finding was obtained in 2 independent patient series, which makes it worthy validating in further studies for this most difficult to treat breast cancer patient subset. Citation Format: Vassiliki Kotoula, Sotiris Lakis, Kyriaki Papadopoulou, Ioannis Vlachos, Eleni Giannoulatou, Zoi Alexopoulou, Eleni Timotheadou, Ioannis Efstratiou, Flora Zagouri, George Pentheroudakis, Helen Gogas, Spyros Miliaras, Maria Sotiropoulou, George Zografos, Dimitrios Pectasides, George Fountzilas. A role for mutated hydrophobic amino acids in patients with triple-negative breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 538.
- Published
- 2016
46. A randomized phase III trial of adjuvant chemotherapy with irinotecan, leucovorin and fluorouracil versus leucovorin and fluorouracil for stage II and III colon cancer: A Hellenic Cooperative Oncology Group study
- Author
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Ioannis Efstratiou, Nikolaos Xiros, George Fountzilas, Meletios A. Dimopoulos, Georgia Kafiri, Theofanis Economopoulos, Dimitrios Pectasides, Aristotelis Bamias, Pavlos Papakostas, Dimosthenis Miliaras, Epaminontas Samantas, Irene Papaspirou, Dimitrios Bafaloukos, Maria Karina, Christos Papadimitriou, G. Klouvas, Ippokratis Korantzis, Lia Malettou, Gerasimos Aravantinos, F. Matsiakou, George Basdanis, George Pentheroudakis, Charisios Karanikiotis, Thomas Makatsoris, Nikolaos Pisanidis, and Haralabos P. Kalofonos
- Subjects
Male ,Oncology ,Colorectal cancer ,medicine.medical_treatment ,Leucovorin ,lcsh:Medicine ,Kaplan-Meier Estimate ,derivatives/therapeutic use ,Antineoplastic Combined Chemotherapy Protocols ,Medicine(all) ,Greece ,General Medicine ,Middle Aged ,Antineoplastic Agents/*therapeutic use ,Treatment Outcome ,Chemotherapy, Adjuvant ,Fluorouracil ,Colonic Neoplasms ,Female ,Bolus (digestion) ,effects/*therapeutic use ,Research Article ,medicine.drug ,Adult ,medicine.medical_specialty ,Camptothecin/administration & dosage/adverse effects/*analogs & ,Antineoplastic Agents ,Neutropenia ,Irinotecan ,Young Adult ,Fluorouracil/administration & dosage/adverse effects/*therapeutic use ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols/administration & dosage/adverse ,medicine ,Humans ,Leucovorin/administration & dosage/adverse effects/*therapeutic use ,Aged ,Neoplasm Staging ,Chemotherapy ,Dose-Response Relationship, Drug ,business.industry ,lcsh:R ,medicine.disease ,Clinical trial ,Colonic Neoplasms/*drug therapy/*pathology ,Camptothecin ,business - Abstract
Background Colon cancer is a public health problem worldwide. Adjuvant chemotherapy after surgical resection for stage III colon cancer has been shown to improve both progression-free and overall survival, and is currently recommended as standard therapy. However, its value for patients with stage II disease remains controversial. When this study was designed 5-fluorouracil (5FU) plus leucovorin (LV) was standard adjuvant treatment for colon cancer. Irinotecan (CPT-11) is a topoisomerase I inhibitor with activity in metastatic disease. In this multicenter adjuvant phase III trial, we evaluated the addition of irinotecan to weekly 5FU plus LV in patients with stage II or III colon cancer. Methods The study included 873 eligible patients. The treatment consisted of weekly administration of irinotecan 80 mg/m2 intravenously (IV), LV 200 mg/m2 and 5FU 450 mg/m2 bolus (Arm A) versus LV 200 mg/m2 and 5FU 500 mg/m2 IV bolus (Arm B). In Arm A, treatments were administered weekly for four consecutive weeks, followed by a two-week rest, for a total of six cycles, while in Arm B treatments were administered weekly for six consecutive weeks, followed by a two-week rest, for a total of four cycles. The primary end-point was disease-free survival (DFS) at three years. Results The probability of overall survival (OS) at three years was 0.88 for patients in Arm A and 0.86 for those in Arm B, while the five-year OS probability was 0.78 and 0.76 for patients in Arm A and Arm B, respectively (P = 0.436). Furthermore, the probability of DFS at three years was 0.78 and 0.76 for patients in Arm A and Arm B, respectively (P = 0.334). With the exception of leucopenia and neutropenia, which were higher in patients in Arm A, there were no significant differences in Grades 3 and 4 toxicities between the two regimens. The most frequently recorded Grade 3/4 toxicity was diarrhea in both treatment arms. Conclusions Irinotecan added to weekly bolus 5FU plus LV did not result in improvement in disease-free or overall survival in stage II or III colon cancer, but did increase toxicity. Trial registration Australian New Zealand Clinical Trials Registry: ACTRN12610000148077
- Published
- 2011
47. Hyperpigmented forearms and nail: a quiz
- Author
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Dimitrios Kalabalikis, Ioannis Efstratiou, Paraskevi Pitsari, Myrto-Gerorgia Trakatelli, Aikaterini Patsatsi, and Dimitrios Sotiriadis
- Subjects
medicine.medical_specialty ,business.industry ,Biopsy ,Dermatology ,General Medicine ,Hemosiderin ,Forearm ,Nail Diseases ,medicine.anatomical_structure ,Hyperpigmentation ,medicine ,Nail (anatomy) ,Lupus Erythematosus, Cutaneous ,Humans ,Female ,business ,Aged ,Hydroxychloroquine ,Skin - Published
- 2010
48. Ectopic Cushing's syndrome due to CRH secreting liver metastasis in a patient with medullary thyroid carcinoma
- Author
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Kalliopi Pazaitou-Panayiotou, Frideriki Patakiouta, Eleni Georgiou, Ioannis Efstratiou, Maria Boudina, Alexandra Chrisoulidou, Iraklis Vainas, Ioannis Iakovou, and George Kontogeorgos
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Male ,endocrine system ,Pathology ,medicine.medical_specialty ,Medullary cavity ,Hydrocortisone ,Corticotropin-Releasing Hormone ,Endocrinology, Diabetes and Metabolism ,Biopsy, Fine-Needle ,Metastasis ,Thyroid carcinoma ,Treatment Refusal ,Fatal Outcome ,Adrenocorticotropic Hormone ,Biopsy ,Carcinoma ,medicine ,Humans ,Thyroid Neoplasms ,Cushing Syndrome ,medicine.diagnostic_test ,biology ,business.industry ,Liver Neoplasms ,General Medicine ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Fine-needle aspiration ,Calcitonin ,Carcinoma, Medullary ,Hormones, Ectopic ,Synaptophysin ,biology.protein ,business ,hormones, hormone substitutes, and hormone antagonists - Abstract
Ectopic production of CRH by a medullary thyroid carcinoma or its metastases is a rare cause of ectopic Cushing’s syndrome (ECS). We report a 45-year old male with medullary thyroid carcinoma (MTC), who, 24 years following the initial diagnosis, presented with clinical and biochemical evidence of an ACTH dependent Cushing’s syndrome. Rapid deterioration of his clinical condition and elevated cortisol levels were observed. Computed tomographic imaging of the abdomen revealed extensive liver metastases. The patient underwent fine needle aspiration biopsy of a liver lesion and immunohistochemistry showed that the cells expressed calcitonin, carcino-embryonic antigen and synaptophysin. Further analysis revealed that the material also expressed CRH. This is an unusual case of a CRH-secreting liver metastasis from a medullary thyroid carcinoma 24 years after the initial diagnosis of MTC.
- Published
- 2008
49. Congenital cystic eye with multiple dermal appendages and intracranial congenital anomalies: report of a case
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Ioannis Efstratiou, Mary Arvanity, Styliani Spyridi, Ioannis Tsitouridis, Christos Tsantiridis, and Michael Michaelides
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Appendage ,Anophthalmia ,medicine.diagnostic_test ,business.industry ,Invagination ,Magnetic resonance imaging ,Anatomy ,Optic vesicle ,medicine.disease ,eye diseases ,medicine ,Radiology, Nuclear Medicine and imaging ,Cyst ,Cardiology and Cardiovascular Medicine ,business - Abstract
Congenital cystic eye (anophthalmia with cyst) is an extremely rare anomaly discovered at birth with few reported cases in the literature, resulting from partial or complete failure during invagination of the primary optic vesicle during fetal development. Herein we present the radiographic, ultrasound, and magnetic resonance imaging findings of a unique case of congenital cystic eye associated with dermal appendages and advanced intracranial congenital anomalies in a 3-month-old boy.
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- 2008
50. Significance of PIK3CA Mutations in Patients with Early Breast Cancer Treated with Adjuvant Chemotherapy: A Hellenic Cooperative Oncology Group (HeCOG) Study
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Elpida Charalambous, George Papaxoinis, Maria Skondra, Dimitrios Bafaloukos, Thomas Zaramboukas, Eleni Timotheadou, Gerasimos Aravantinos, Angelos Koutras, Konstantine T. Kalogeras, Helen Patsea, Kyriaki Papadopoulou, George Pentheroudakis, Ioannis Varthalitis, Christos Christodoulou, Flora Zagouri, Helen Gogas, Paris Kosmidis, Pavlos Papakostas, Vassiliki Kotoula, Ioannis Efstratiou, Zoi Alexopoulou, George Fountzilas, Dimitrios Pectasides, and Chrisoula D. Scopa
- Subjects
Adult ,Oncology ,medicine.medical_specialty ,Mutation rate ,Low protein ,Class I Phosphatidylinositol 3-Kinases ,lcsh:Medicine ,Breast Neoplasms ,Biology ,medicine.disease_cause ,Phosphatidylinositol 3-Kinases ,Young Adult ,Exon ,symbols.namesake ,Breast cancer ,Mutation Rate ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,PTEN ,lcsh:Science ,neoplasms ,Aged ,Neoplasm Staging ,Sanger sequencing ,Mutation ,Multidisciplinary ,lcsh:R ,Middle Aged ,Prognosis ,medicine.disease ,Chemotherapy, Adjuvant ,biology.protein ,symbols ,Immunohistochemistry ,Female ,lcsh:Q ,Research Article ,Signal Transduction - Abstract
Background The PI3K-AKT pathway is frequently activated in breast cancer. PIK3CA mutations are most frequently found in the helical (exon 9) and kinase (exon 20) domains of this protein. The aim of the present study was to examine the role of different types of PIK3CA mutations in combination with molecular biomarkers related to PI3K-AKT signaling in patients with early breast cancer. Methods Tumor tissue samples from 1008 early breast cancer patients treated with adjuvant chemotherapy in two similar randomized trials of HeCOG were examined. Tumors were subtyped with immunohistochemistry (IHC) and FISH for ER, PgR, Ki67, HER2 and androgen receptor (AR). PIK3CA mutations were analyzed by Sanger sequencing (exon 20) and qPCR (exon 9) (Sanger/qPCR mutations). In 610 cases, next generation sequencing (NGS) PIK3CA mutation data were also available. PIK3CA mutations and PTEN protein expression (IHC) were analyzed in luminal tumors (ER and/or PgR positive), molecular apocrine carcinomas (MAC; ER/PgR negative / AR positive) and hormone receptor (ER/PgR/AR) negative tumors. Results PIK3CA mutations were detected in 235/1008 tumors (23%) with Sanger/qPCR and in 149/610 tumors (24%) with NGS. Concordance between the two methods was good with a Kappa coefficient of 0.76 (95% CI 0.69–0.82). Lobular histology, low tumor grade and luminal A tumors were associated with helical domain mutations (PIK3CAhel), while luminal B with kinase domain mutations (PIK3CAkin). The overall incidence of PIK3CA mutations was higher in luminal as compared to MAC and hormone receptor negative tumors (p = 0.004). Disease-free and overall survival did not significantly differ with respect to PIK3CA mutation presence and type. However, a statistically significant interaction between PIK3CA mutation status and PTEN low protein expression with regard to prognosis was identified. Conclusions The present study did not show any prognostic significance of specific PIK3CA mutations in a large group of predominantly lymph-node positive breast cancer women treated with adjuvant chemotherapy. Further analyses in larger cohorts are warranted to investigate possible differential effect of distinct PIK3CA mutations in small subgroups of patients.
- Published
- 2015
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