30 results on '"Thodou, Eleni"'
Search Results
2. Somatostatin receptor profile in pituitary thyrotroph adenomas
- Author
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Thodou, Eleni and Kontogeorgos, George
- Published
- 2020
- Full Text
- View/download PDF
3. MGMT immunohistochemistry in pituitary tumors: controversies with clinical implications
- Author
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Kontogeorgos, George, Thodou, Eleni, Koutourousiou, Mary, Kaltsas, Gregory, and Seretis, Andreas
- Published
- 2019
- Full Text
- View/download PDF
4. Is MGMT the best marker to predict response of temozolomide in aggressive pituitary tumors? Alternative markers and prospective treatment modalities
- Author
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Kontogeorgos, George and Thodou, Eleni
- Published
- 2019
- Full Text
- View/download PDF
5. Gastric Cancer in the Era of Epigenetics.
- Author
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Christodoulidis, Grigorios, Koumarelas, Konstantinos-Eleftherios, Kouliou, Marina-Nektaria, Thodou, Eleni, and Samara, Maria
- Subjects
CIRCULAR RNA ,STOMACH cancer ,EPIGENETICS ,LINCRNA ,DNA methyltransferases ,METABOLIC reprogramming - Abstract
Gastric cancer (GC) remains a significant contributor to cancer-related mortality. Novel high-throughput techniques have enlightened the epigenetic mechanisms governing gene-expression regulation. Epigenetic characteristics contribute to molecular taxonomy and give rise to cancer-specific epigenetic patterns. Helicobacter pylori (Hp) infection has an impact on aberrant DNA methylation either through its pathogenic CagA protein or by inducing chronic inflammation. The hypomethylation of specific repetitive elements generates an epigenetic field effect early in tumorigenesis. Epstein–Barr virus (EBV) infection triggers DNA methylation by dysregulating DNA methyltransferases (DNMT) enzyme activity, while persistent Hp-EBV co-infection leads to aggressive tumor behavior. Distinct histone modifications are also responsible for oncogene upregulation and tumor-suppressor gene silencing in gastric carcinomas. While histone methylation and acetylation processes have been extensively studied, other less prevalent alterations contribute to the development and migration of gastric cancer via a complex network of interactions. Enzymes, such as Nicotinamide N-methyltransferase (NNMT), which is involved in tumor's metabolic reprogramming, interact with methyltransferases and modify gene expression. Non-coding RNA molecules, including long non-coding RNAs, circular RNAs, and miRNAs serve as epigenetic regulators contributing to GC development, metastasis, poor outcomes and therapy resistance. Serum RNA molecules hold the potential to serve as non-invasive biomarkers for diagnostic, prognostic or therapeutic applications. Gastric fluids represent a valuable source to identify potential biomarkers with diagnostic use in terms of liquid biopsy. Ongoing clinical trials are currently evaluating the efficacy of next-generation epigenetic drugs, displaying promising outcomes. Various approaches including multiple miRNA inhibitors or targeted nanoparticles carrying epigenetic drugs are being designed to enhance existing treatment efficacy and overcome treatment resistance. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
6. Double adenomas of the pituitary: an imaging, pathological, and clinical diagnostic challenge
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Kontogeorgos, George and Thodou, Eleni
- Published
- 2019
- Full Text
- View/download PDF
7. Characterization of a miRNA Signature with Enhanced Diagnostic and Prognostic Power for Patients with Bladder Carcinoma.
- Author
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Samara, Maria, Vlachostergios, Panagiotis J., Thodou, Eleni, Zachos, Ioannis, Mitrakas, Lampros, Evmorfopoulos, Konstantinos, Tzortzis, Vassilios, and Giakountis, Antonis
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MICRORNA ,CELL cycle regulation ,GENE expression ,CANCER diagnosis ,CARCINOMA ,BODY fluids - Abstract
Bladder carcinoma is globally among the most prevalent cancers and is associated with a high mortality rate at advanced stages. Its detection relies on invasive diagnostic methods that are unpleasant for the patient. Non-invasive molecular biomarkers, such as miRNAs, could serve as alternatives for early detection and prognosis of this malignancy. We designed a computational approach that combines transcriptome profiling, survival analyses, and calculation of diagnostic power in order to isolate miRNA signatures with high diagnostic and prognostic utility. Our analysis of TCGA-BLCA data from 429 patients yielded one miRNA signature, consisting of five upregulated and three downregulated miRNAs with cumulative diagnostic power that outperforms current diagnostic methods. The same miRNAs have a strong prognostic significance since their expression is associated with the overall survival of bladder cancer patients. We evaluated the expression of this signature in 19 solid cancer types, supporting its unique diagnostic utility for bladder carcinoma. We provide computational evidence regarding the functional implications of this miRNA signature in cell cycle regulation, demonstrating its abundance in body fluids, including peripheral blood and urine. Our study characterized a novel miRNA signature with the potential to serve as a non-invasive method for bladder cancer diagnosis and prognosis. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
8. The Genomic Signatures of Linitis Plastica Signal the Entrance into a New Era: Novel Approaches for Diagnosis and Treatment.
- Author
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Christodoulidis, Grigorios, Koumarelas, Konstantinos Eleftherios, Kouliou, Marina Nektaria, Samara, Maria, Thodou, Eleni, and Zacharoulis, Dimitris
- Subjects
STROMAL cells ,TIGHT junctions ,DIAGNOSIS ,DRUG target ,BIOMARKERS ,PHARMACOGENOMICS - Abstract
Linitis Plastica (LP) is a rare and aggressive tumor with a distinctive development pattern, leading to the infiltration of the gastric wall, the thickening of the gastric folds and a "leather bottle appearance". LP is an extremely heterogeneous tumor caused by mutations in oncogenic and tumor suppressive genes, as well as molecular pathways, along with mutations in stromal cells and proteins related to tight junctions. Elucidating the molecular background of tumorigenesis and clarifying the correlation between cancerous cells and stromal cells are crucial steps toward discovering novel diagnostic methods, biomarkers and therapeutic targets/agents. Surgery plays a pivotal role in LP management, serving both as a palliative and curative procedure. In this comprehensive review, we aim to present all recent data on the molecular background of LP and the novel approaches to its management. [ABSTRACT FROM AUTHOR]
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- 2023
- Full Text
- View/download PDF
9. The impact of cryopreservation on both sperm HPV-negative and positive subtypes.
- Author
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Anagnostou, Maria, Samara, Maria, Thodou, Eleni, Messini, Christina I., Dafopoulos, Konstantinos, Chatzimeletiou, Katerina, Dovolou, Eleni, Daponte, Alexandros, Koukoulis, George, and Anifandis, George
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SPERMATOZOA ,HUMAN papillomavirus ,SEMEN analysis ,SEMEN - Abstract
It is well known that various human papillomavirus (HPV) genotypes are present in semen specimens. Also, it has been demonstrated that sperm parameters are negatively affected when HPV infection is present in the sperm sample. Besides all these, the effect of cryopreservation on HPV sensitivity and resistance is not known. The aim of the present study is to evaluate first the prevalence of HPV and secondly to elucidate whether cryopreservation of sperm HPV-positive samples has any effect on the viability of HPV. For this purpose, a cohort of 78 sperm specimens was used from a respective number of patients. After giving informed consent, semen analysis was performed. Each sperm sample was divided into four equal aliquots. The first one (fresh) was evaluated for the prevalence of HPV, while the other three aliquots were cryopreserved by adding an equal quantity of cryoprotectant and plunged into the LN. Each of the three aliquots was thawed 3, 6, and 12 months later, respectively, so as to evaluate whether there is a time-resistance period of HPV prevalence. HPV infection was found to be in eleven sperm samples, demonstrating a 14.1% (11/78) HPV prevalence. Among the HPV-positive samples, six of them were high-risk and the remaining were low-risk genotypes. Moreover, the high-risk fresh samples demonstrated higher motility values than the low-risk samples (60% ± 2.7 vs 45.6% ± 3.7, p <.05), while semen volume in the high-risk samples was significantly lower than the respective volume in the low-risk samples (2.26 ± 0.2ml vs 3.5 ± 0.6ml, p <.05). Interestingly, cryopreservation of the HPV-positive samples resulted in the sustainability and time-resistance of HPV in all high-risk HPV-positive samples, something that was not the case with the low-risk HPV-positive samples. Conclusively, sperm samples infected with high-risk HPV, demonstrate lower sperm parameters and time-resistance activity during cryopreservation. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
10. The gonadotroph origin of null cell adenomas
- Author
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Kontogeorgos, George and Thodou, Eleni
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- 2016
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11. High-risk pituitary adenomas and strategies for predicting response to treatment
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Kontogeorgos, George Thodou, Eleni Osamura, Robert Y. Lloyd, V, Ricardo
- Abstract
High-risk pituitary adenomas are aggressive. They show clinical and imaging features similar to those of carcinomas, including infiltration of the surrounding brain structures, but lack cerebrospinal or systemic metastases. In addition, they display distinct behavior, including tendency for fast growth and frequent recurrences, which are difficult to control. The term “high-risk” adenoma was first introduced in the 4th edition of the World Health Organization Classification of Endocrine Tumors in 2017. Five defined adenoma types belong to this category, including sparsely granulated somatotroph, lactotroph in men, Crooke cell, silent corticotroph, and plurihormonal PIT-1 positive adenomas. The morphological and immunohistochemical characteristics of high-risk adenomas are herein described in detail. In addition, the clinical features and the treatment options are presented. This review focuses on predictive markers assessed by immunohistochemistry, which help clinicians to design the appropriate treatment strategies for high-risk adenomas. Somatostatin receptor status predicts effectiveness of postsurgical treatment with somatostatin analogs, and MGMT expression predicts response to treatment with temozolomide. This comprehensive review presents the clinical and pathological features of high-risk pituitary adenomas, underlines the contribution of immunohistochemistry, and emphasizes the leading role of pathology in the design of optimal clinical management.
- Published
- 2022
12. Association of Pathology Markers with Somatostatin Analogue Responsiveness in Acromegaly.
- Author
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Kontogeorgos, George, Markussis, Vyron, Thodou, Eleni, Kyrodimou, Efi, Choreftaki, Theodossia, Nomikos, Panagiotis, Lampropoulos, Kostas I., and Tsagarakis, Stylianos
- Subjects
THERAPEUTIC use of antineoplastic agents ,DRUG efficacy ,PITUITARY gland ,IMMUNOHISTOCHEMISTRY ,RETROSPECTIVE studies ,SURGERY ,PATIENTS ,REGRESSION analysis ,GROWTH hormone-secreting pituitary adenoma ,PRE-tests & post-tests ,CANCER patients ,CELLULAR signal transduction ,SOMATOSTATIN ,ACROMEGALY ,DNA-binding proteins ,CELL adhesion molecules ,TUMOR markers ,TRANSCRIPTION factors ,NEUROTRANSMITTER receptors - Abstract
Background. Somatotroph adenomas (SAs) exhibit a variable responsiveness to somatostatin analogue (SS-a) treatment, a process that is not well understood. We investigated established and novel histological markers as predictors of SS-a responsiveness. Methods. We retrospectively investigated pathology samples from 36 acromegalic patients that underwent transsphenoidal surgery. Clinical, hormonal, and imaging data were available in 24/36 patients, before and after SS-a treatment. Specimens were semiquantitatively analyzed with immunocytochemistry for Ki-67, KER, SSTR-2, SSTR-5, ZAC-1, E-cadherin, and AIP. Results. Collectively, 18 (50%) adenomas were each classified as densely/sparsely granulated somatotroph adenomas (DGSAs/SGSAs), respectively. Patients that received preoperative SS-a had lower expression of SSTR-2 compared to those that did not (2.0 (1.0, 3.0) vs. 3.0 (3.0, 3.0), p = 0.042). Compared with DGSAs, SGSAs had higher Ki-67 labeling index (LI) (1.0 (0.5, 1.0) vs. 2.0 (1.0, 3.5), p = 0.013), and a higher proportion of high MR T2 signal (1 (6%) vs. 6 (33%), p = 0.035), and tended to express less ZAC-1 (p = 0.061) and E-cadherin (p = 0.067). In linear regression corrected for baseline growth hormone (GH), ZAC-1 immunostaining was significantly associated with a decrease in GH levels after SS-a treatment (beta (95% confidence interval): −1.53 (−2.80, −0.26), p = 0.021). No markers were associated with changes in circulating insulin-like growth factor-I (IGF-I) after treatment with SS-a. Conclusion. The novel marker ZAC-1 was associated with GH response to medical treatment with SS-a. The SGSA cases were characterized by higher Ki-67 values and MR T2 signals indicative of an inferior response to SS-a. These findings improve our understanding of the mechanisms underlying SA response to medical treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
13. Insights into the Role of Telomeres in Human Embryological Parameters. Opinions Regarding IVF
- Author
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Anifandis, George Samara, Maria Simopoulou, Mara Messini, Christina I. Chatzimeletiou, Katerina Thodou, Eleni Daponte, Alexandros Georgiou, Ioannis
- Abstract
Telomeres promote genome integrity by protecting chromosome ends from the activation of the DNA damage response and protecting chromosomes from the loss of coding sequences due to the end replication problem. Telomere length (TL) is progressively shortened as age progresses, thus resulting in cellular senescence. Therefore, TL is in strong adverse linear correlation with aging. Mounting evidence supports the notion that telomeres and male/female infertility are in a close relationship, posing the biology of telomeres as a hot topic in the era of human-assisted reproduction. Specifically, the length of sperm telomeres is gradually increasing as men get older, while the telomere length of the oocytes seems not to follow similar patterns with that of sperm. Nonetheless, the telomere length of the embryos during the cleavage stages seems to have a paternal origin, but the telomere length can be further extended by telomerase activity during the blastocyst stage. The latter has been proposed as a new molecular biomarker with strong predictive value regarding male infertility. As far as the role of telomeres in assisted reproduction, the data is limited but the length of telomeres in both gametes seems to be affected mainly by the cause of infertility rather than the assisted reproductive therapy (ART) procedure itself. The present review aims to shed more light into the role of telomeres in human embryological parameters, including gametes and embryos and also presents opinions regarding the association between telomeres and in vitro fertilization (IVF).
- Published
- 2021
14. Small-Cell Malignancies of Thyroid: Challenge Solved?
- Author
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Canberk, Sule, Thodou, Eleni, and Bongiovanni, Massimo
- Published
- 2022
- Full Text
- View/download PDF
15. Prolactin-producing pituitary adenoma with incomplete neuronal transformation: an intermediate adenoma–neuronal tumor
- Author
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Thodou, Eleni, Kontogeorgos, George, Horvath, Eva, and Kovacs, Kalman
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- 2004
- Full Text
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16. Structure-function correlations of growth hormone or/and prolactin-producing pituitary adenomas: An in vitro study with the reverse hemolytic plaque assay
- Author
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Thodou, Eleni, Kontogeorgos, G., Kyrodimou, E., Salla, H., Ramyar, L., Vamvassakis, E., Piaditis, G., Anagnostopoulos, N., Tzanis, S., Levedis, A., Rologis, D., and Asa, S. L.
- Published
- 1999
- Full Text
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17. Immunocytochemical Accumulation of p53 in Corticotroph Adenomas: Relationship with Heat Shock Proteins and Apoptosis
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Kontogeorgos, George, Kapranos, Nikiforos, Thodou, Eleni, Sambaziotis, Demetrios, and Tsagarakis, Stylianos
- Published
- 1999
- Full Text
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18. Hodgkin Lymphoma Mimicking Inflammatory Breast Carcinoma: A Rare Case with Diagnostic Challenge and Novel Treatment
- Author
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Thodou, Eleni, Befani, Maria, Triantafyllidis, George, Choreftaki, Theodosia, Kanellis, George, and Giannakoulas, Nikolaos
- Subjects
Article Subject ,hemic and lymphatic diseases ,skin and connective tissue diseases - Abstract
Extranodal Hodgkin lymphoma involving the breast is infrequent. Most cases reported in the literature were diagnosed by histology after lumpectomy. We present a Hodgkin lymphoma mimicking inflammatory breast carcinoma in a 57-year-old woman. The diagnosis was performed by fine-needle aspiration (FNA) of the breast lesion and the axillary lymph nodes with rapid on-site evaluation followed by immunocytochemistry, and it was confirmed by histology. The patient after first-line chemotherapy developed relapse/refractory disease. Salvage chemotherapy regimens were applied with poor results and severe toxicity. Total remission was achieved with monotherapy of brentuximab vedotin, a novel anti-CD30-targeted antibody drug conjugate. This is a unique case of breast HL with misleading clinical presentation initially diagnosed by cytology. FNA as a minimally invasive diagnostic tool was crucial in avoiding unnecessary breast surgery and further delay of chemotherapy. It is also the first report highlighting the importance of this novel immunotherapy in the management of refractory Hodgkin lymphoma with breast involvement.
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- 2019
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19. A serum-free system for primary cultures of human pituitary adenomas
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Thodou, Eleni, Ramyar, Lily, Cohen, Arthur I., Singer, William, and Asa, Sylvia L.
- Published
- 1995
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20. Challenges in Cytology Specimens With Hürthle Cells.
- Author
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Thodou, Eleni, Canberk, Sule, and Schmitt, Fernando
- Subjects
CYTOLOGY ,CELL tumors ,NEEDLE biopsy ,THYROID cancer ,DIAGNOSIS ,DIFFERENTIAL diagnosis - Abstract
In fine-needle aspirations (FNA) of thyroid, Hürthle cells can be found in a broad spectrum of lesions, ranging from non-neoplastic conditions to aggressive malignant tumors. Recognize them morphologically, frequently represents a challenging for an adequately diagnosis and are associated with a significant interobserver variability. Although the limitations of the morphologic diagnosis still exist, the interpretation of the context where the cells appear and the recent advances in the molecular knowledge of Hürthle cells tumors are contributing for a more precise diagnosis. This review aims to describe the cytology aspects of all Hürthle cells neoplastic and non-neoplastic thyroid lesions, focusing on the differential diagnosis and reporting according to The Bethesda System for Reporting Thyroid Cytology (TBSRTC). New entities according to the latest World Health Organization (WHO) classification are included, as well as an update of the current molecular data. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
21. A Rapidly Growing Thyroid Nodule: A Diagnostic Challenge in Fine Needle Aspiration.
- Author
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Thodou, Eleni, Sarantopoulou, Chrysanthi, Psachoulia, Charalambia, Ravazoula, Panagiota, Armoni, Athanasia, and Schmitt, Fernando C.
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- 2020
- Full Text
- View/download PDF
22. Insights into the Role of Telomeres in Human Embryological Parameters. Opinions Regarding IVF.
- Author
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Anifandis, George, Samara, Maria, Simopoulou, Mara, Messini, Christina I., Chatzimeletiou, Katerina, Thodou, Eleni, Daponte, Alexandros, and Georgiou, Ioannis
- Subjects
TELOMERES ,FERTILIZATION in vitro ,HUMAN in vitro fertilization ,REPRODUCTIVE technology ,MALE infertility ,FEMALE infertility ,CELLULAR aging - Abstract
Telomeres promote genome integrity by protecting chromosome ends from the activation of the DNA damage response and protecting chromosomes from the loss of coding sequences due to the end replication problem. Telomere length (TL) is progressively shortened as age progresses, thus resulting in cellular senescence. Therefore, TL is in strong adverse linear correlation with aging. Mounting evidence supports the notion that telomeres and male/female infertility are in a close relationship, posing the biology of telomeres as a hot topic in the era of human-assisted reproduction. Specifically, the length of sperm telomeres is gradually increasing as men get older, while the telomere length of the oocytes seems not to follow similar patterns with that of sperm. Nonetheless, the telomere length of the embryos during the cleavage stages seems to have a paternal origin, but the telomere length can be further extended by telomerase activity during the blastocyst stage. The latter has been proposed as a new molecular biomarker with strong predictive value regarding male infertility. As far as the role of telomeres in assisted reproduction, the data is limited but the length of telomeres in both gametes seems to be affected mainly by the cause of infertility rather than the assisted reproductive therapy (ART) procedure itself. The present review aims to shed more light into the role of telomeres in human embryological parameters, including gametes and embryos and also presents opinions regarding the association between telomeres and in vitro fertilization (IVF). [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
23. Investigation of somatostatin receptor profile of neuroendocrine carcinomas of the breast.
- Author
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Kontogeorgos, George, Thodou, Eleni, and Choreftaki, Theodosia
- Subjects
- *
SOMATOSTATIN receptors , *CARCINOMA - Abstract
Carcinomas of the breast with neuroendocrine features are rare primary neoplasms positive for neuroendocrine markers. According to the WHO classification of tumours of the breast they are divided into three morphologically distinct categories. They comprise neuroendocrine tumour (NET), neuroendocrine carcinoma (NEC) and carcinoma with neuroendocrine differentiation (NED). The purpose of this study was to investigate for the first time the full spectrum of sstr expression status in breast carcinomas with neuroendocrine features. Fifteen primary breast carcinomas with histological and immunohistochemical neuroendocrine features were studied. Four of them were classified as NETs and two as NECs, and the remaining 9 as carcinomas with NED. All six types of somatostatin receptor (sstr) types (sstr1, sstr 2A, sstr2B, sstr3, sstr4 and sstr5) were investigated by immunohistochemistry. To assess the distribution and intensity of membranous receptor immunoreactivity, a four-scale scoring system was used. Overall predominant receptors were sstr2A, sstr2B, sstr3 and sstr5 showing the highest membranous staining scores 3+ and 2 +. The sstr1 was not detected. Given that carcinomas with neuroendocrine features represent distinct entities, patients with such tumours may benefit from sstr targeting therapies. Immunohistochemistry for sstrs can predict the effectiveness of administration of SST analogues to those patients, thus contributing to achieve the maximum therapeutic outcome, particularly in NETs and NECs with scores 2+ and 3 +. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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- View/download PDF
24. Evaluation of a cytology-molecular co-test in liquid-based cytology-processed urine for defining indeterminate categories of the Paris system.
- Author
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Samara M, Thodou E, Apostolopoulou C, Vlachostergios PJ, Mitrakas L, Zachos I, Anagnostou M, Koukoulis G, and Tzortzis V
- Abstract
Introduction: Urine cytology using the Paris system (TPS) classification is useful for the detection and monitoring of bladder urothelial carcinoma (UC). However, the categories "Atypical Urothelial Cells" (AUC) and "Suspicious for High-Grade Urothelial Carcinoma" (SHGUC) do not establish a clear diagnosis. This pilot study aimed to investigate whether the presence of mutations in fibroblast growth factor receptor 3 (FGFR3) and telomerase reverse transcriptase (TERT) genes, in urine processed with liquid-based cytology (LBC) could enhance the diagnostic performance of cytology, particularly in defining the indeterminate categories of AUC and SHGUC., Methods: Urine samples from 82 UC patients with primary tumors or under surveillance and 10 healthy individuals were examined. The THIN PREP method was used for cytology followed by DNA isolation from urine sediments. Targeted molecular analysis was achieved in 70 cases (63 patients and 7 controls) for exons 7 and 10 of the FGFR3 gene and the TERT gene promoter (pTERT), using PCR and Sanger sequencing. Molecular results were correlated with TPS cytology categories and validated by histopathological findings following cystoscopy., Results: In healthy subjects, cytology was negative for high-grade urothelial carcinoma (NHGUC) and no mutations were found. No mutations were found in patients with NHGUC cytology, except for one case with equivocal cystoscopy that carried a pTERT mutation. In high-grade urothelial carcinoma cytology (HGUC) (15/20, 75%) of the cases with histologically confirmed UC, molecular analysis revealed the presence of pTERT without FGFR3 mutations. In SHGUC and AUC cytology, FGFR3 and/or pTERT mutations were detected in (3/4, 75%) and 4/4 (100%) histologically confirmed UC cases, respectively. Cytology sensitivity was 85.7% increasing to 100% with the combined cytology-molecular test, whereas specificity remained unchanged at 86.3%., Conclusions: This pilot study suggests that the incorporation of FGFR3/pTERT molecular testing in urine LBC could enhance the diagnostic value of cytology by diagnosing BUC in indeterminate cytology categories., (S. Karger AG, Basel.)
- Published
- 2024
- Full Text
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25. Mutational profile of primary clear cell renal cell carcinoma predicts recurrence and potential candidacy for adjuvant immune checkpoint inhibition.
- Author
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Vlachostergios PJ, Papathanassiou M, Anagnostou M, Thodou E, Tamposis I, Mitrakas L, Zachos I, Koukoulis GK, Samara M, and Tzortzis V
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Tumor Suppressor Proteins genetics, Ataxia Telangiectasia Mutated Proteins genetics, Von Hippel-Lindau Tumor Suppressor Protein genetics, Prognosis, Histone-Lysine N-Methyltransferase genetics, Adult, Transcription Factors genetics, Aged, 80 and over, Nuclear Proteins genetics, High-Throughput Nucleotide Sequencing, DNA-Binding Proteins, Histone Demethylases, Carcinoma, Renal Cell genetics, Carcinoma, Renal Cell pathology, Carcinoma, Renal Cell mortality, Kidney Neoplasms genetics, Kidney Neoplasms pathology, Mutation, Immune Checkpoint Inhibitors therapeutic use, Ubiquitin Thiolesterase genetics, Neoplasm Recurrence, Local genetics
- Abstract
Background: The risk of recurrence after nephrectomy for primary clear cell renal cell carcinoma (ccRCC) is estimated in daily practice solely based on clinical criteria. The aim of this study was to assess the prognostic relevance of common somatic mutations with respect to tumor aggressiveness and outcomes of ccRCC patients after definitive treatment., Methods: Primary tumors from 37 patients with ccRCC who underwent radical nephrectomy were analyzed for presence of somatic mutations using a 15-gene targeted next-generation sequencing (NGS) panel. Associations to histopathologic characteristics and outcomes were investigated in the study cohort (n=37) and validated in The Cancer Genome Atlas (TCGA) ccRCC cohort (n=451)., Results: VHL was the most frequently mutated gene (51%), followed by PBRM1 (27%), BAP1 (13%), SETD2 (13%), KDM5C (5%), ATM (5%), MTOR (5%), and PTEN (3%). One-third of patients did not have any somatic mutations within the 15-gene panel. The vast majority of tumors harboring no mutations at all or VHL-only mutations (51%) were more frequently of smaller size (pT1-2) and earlier stage (I/II), whereas presence of any other gene mutations in various combinations with or without VHL was enriched in larger (pT3) and higher stage tumors (III) (p=0.02). No recurrences were noted in patients with unmutated tumors or VHL -only mutations as opposed to three relapses in patients with non- VHL somatic mutations (p=0.06). Presence of somatic mutations in PBRM1, BAP1, SETD2, KDM5C, ATM, MTOR , or PTEN genes in 451 TCGA ccRCC patients was associated with a significantly shorter disease-free survival (DFS) compared to those with unaltered tumors (q=0.01)., Conclusions: Preliminary findings from this ongoing study support the prognostic value of non- VHL mutations including PBRM1, BAP1, SETD2, KDM5C, ATM, MTOR , and PTEN in primary ccRCC tumors as surrogates of earlier recurrence and potential selection for adjuvant immune checkpoint inhibition., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Vlachostergios PJ et al.)
- Published
- 2024
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26. Cytological diagnosis of Langerhans cell histiocytosis. Apropos 2 cases.
- Author
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Thodou E, Papaharalambous K, Lappa E, Skliva I, Diamanti E, Kokkinakis G, Konsolaki E, and Tamiolakis D
- Abstract
Langerhans cell histiocytosis (LCH) comprises a wide spectrum of clinical presentations in children and adults, ranging from favorable lesions to aggressive disseminated disease. We present 2 cases where cytology introduced the diagnosis of LCH in the appropriate clinicoradioliogical settings. Cytology can serve accurately in LCH interpretation based on the characteristic cytomorphology and selected immunocytochemistry, so unwarranted biopsy can be overruled and treatment can be adjusted largely where histopathology services are unavailable. Diagnosis may be difficult in cases with scant or insufficient cellular material.
- Published
- 2023
27. Hypoxia-Inducible Factor-2-Altered Urothelial Carcinoma: Clinical and Genomic Features.
- Author
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Vlachostergios PJ, Tamposis IA, Anagnostou M, Papathanassiou M, Mitrakas L, Zachos I, Thodou E, Samara M, and Tzortzis V
- Subjects
- Humans, DNA Copy Number Variations, Genomics, Hypoxia, Neovascularization, Pathologic, RNA, Messenger genetics, RNA, Messenger metabolism, Basic Helix-Loop-Helix Transcription Factors genetics, Carcinoma, Transitional Cell pathology, Urinary Bladder Neoplasms genetics
- Abstract
Background: Hypoxia is recognized as a key feature of cancer growth and is involved in various cellular processes, including proliferation, angiogenesis, and immune surveillance. Besides hypoxia-inducible factor 1-alpha (HIF-1α), which is the main mediator of hypoxia effects and can also be activated under normoxic conditions, little is known about its counterpart, HIF-2. This study focused on investigating the clinical and molecular landscape of HIF-2-altered urothelial carcinoma (UC). Methods: Publicly available next-generation sequencing (NGS) data from muscle-invasive UC cell lines and patient tumor samples from the MSK/TCGA 2020 cohort ( n = 476) were interrogated for the level of expression (mRNA, protein) and presence of mutations, copy number variations, structural variants in the EPAS1 gene encoding HIF-2, and findings among various clinical (stage, grade, progression-free and overall survival) and molecular (tumor mutational burden, enriched gene expression) parameters were compared between altered and unaltered tumors. Results: 19% (7/37) of UC cell lines and 7% (27/380) of patients with muscle-invasive UC display high EPAS1 mRNA and protein expression or/and EPAS1 alterations. EPAS1 -altered tumors are associated with higher stage, grade, and lymph node metastasis as well as with shorter PFS (14 vs. 51 months, q = 0.01) and OS (15 vs. 55 months, q = 0.01). EPAS1 mRNA expression is directly correlated with that of its target-genes, including VEGF, FLT1, KDR, DLL4, CDH5, ANGPT1 ( q < 0.001). While there is a slightly higher tumor mutational burden in EPAS1 -altered tumors (9.9 vs. 4.9 mut/Mb), they are enriched in and associated with genes promoting immune evasion, including ARID5B, SPINT1, AAK1, CLIC3, SORT1, SASH1 , and FGFR3 , respectively ( q < 0.001). Conclusions : HIF-2-altered UC has an aggressive clinical and a distinct genomic and immunogenomic profile enriched in angiogenesis- and immune evasion-promoting genes.
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- 2022
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28. Thyroid Paraganglioma With Medullary Carcinoma: A Unique Combination in a Patient in Association With Multiple Endocrine Neoplasia Type 2B Syndrome With Prolonged Survival.
- Author
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Thodou E, Choreftaki T, Kounadi T, Papanastasiou L, and Kontogeorgos G
- Abstract
Head and neck paragangliomas (PGLs) most commonly derive from the carotid body, jugulotympanic, vagal, and laryngeal paraganglia. Thyroid PGLs originate in the inferior laryngeal paraganglion, which may lie inside the thyroid parenchyma. Intrathyroid PGLs are rare with approximately 75 cases reported to date, mostly as solitary lesions. The coexistence of thyroid PGL with medullary thyroid carcinoma (MTC) has not been reported. Here, we report a unique case of intrathyroid PGL concomitant with MTC in the context of multiple endocrine neoplasia type 2B syndrome. Interestingly, the patient showed a prolonged survival with good clinical response to tyrosine kinase inhibitors, despite her advanced metastatic MTC. We discuss the challenges in pathology, differential diagnosis, and genetic background for the development of these thyroid lesions., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Thodou et al.)
- Published
- 2022
- Full Text
- View/download PDF
29. The gonadotroph origin of null cell adenomas.
- Author
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Kontogeorgos G and Thodou E
- Subjects
- Adenoma classification, Adenoma ultrastructure, Humans, Immunohistochemistry, Microscopy, Electron, Phenotype, Pituitary Neoplasms classification, Pituitary Neoplasms ultrastructure, Terminology as Topic, Adenoma chemistry, Biomarkers, Tumor analysis, Cell Lineage, Follicle Stimulating Hormone, beta Subunit analysis, Glycoprotein Hormones, alpha Subunit analysis, Luteinizing Hormone, beta Subunit analysis, Pituitary Neoplasms chemistry
- Abstract
Objective: The term "null cell" adenoma was first proposed in 1980 to designate pituitary adenomas lacking clinical, biochemical and morphological markers to disclose their cell origin., Design: The aim of this study was to investigate the presence of α- and β-gonadotropin subunits in clinically nonfunctioning pituitary tumors, which were initially immunonegative and thus diagnosed as null cell adenomas. For this reason, we reapplied immunohistochemistry using a more sensitive method comprising a tyramide signal amplification technique, combined with a polymer antibody immunohistochemical detection system., Results: With this approach, all these previously negative tumors became positive for α- and β-gonadotropin hormone subunits., Conclusions: Our results prove that so-called "null cell" adenomas produce α-SU or/and β-FSH or β-LH and therefore are gonadotrph adenomas in origin.
- Published
- 2016
- Full Text
- View/download PDF
30. Galectin-3 as a marker distinguishing functioning from silent corticotroph adenomas.
- Author
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Thodou E, Argyrakos T, and Kontogeorgos G
- Subjects
- ACTH-Secreting Pituitary Adenoma pathology, Adenoma pathology, Humans, Immunohistochemistry, Pituitary Gland metabolism, ACTH-Secreting Pituitary Adenoma diagnosis, Adenoma diagnosis, Biomarkers, Tumor metabolism, Galectin 3 metabolism
- Abstract
Objective: Galectin-3 (Gal-3) belongs to the family of carbohydrate-binding proteins with high affinity for galactoside and is involved in many biological processes including cell growth and differentiation, cell adhesion, tumor progression, apoptosis and metastasis. The aim of this study was to disclose differences in the expression of Gal-3 in silent and functioning corticotroph pituitary adenomas., Design: We examined 30 pituitary adenomas (19 functioning corticotroph, 11 silent corticotroph adenomas). Two prolactinomas and 2 functioning somatotroph adenomas served as positive controls. Antigen retrieval was done by three-minute incubation via pressure boiler in citrate buffer solution, pH 6.0. A polymer was used as a secondary link to DAB chromogen. The independent variables t-test was used for comparison of the mean expression of Gal-3 in the two different corticotroph adenoma subgroups., Results: Eighteen of the functioning corticotroph adenomas (94.73%) were positive for Gal-3 with a cytoplasmic and focally membranous distribution; two cases also exhibited nuclear expression, whereas 9 of the silent corticotroph adenomas (81.81%) had zero or<1% expression of Gal-3 (p=0.001)., Conclusions: Gal-3 is highly expressed in functioning corticotroph adenomas of the pituitary gland, while silent adenomas exhibit very focal to null expression of Gal-3. This observation can be used in the pathological diagnosis to separate functioning from silent corticotroph adenomas of the pituitary.
- Published
- 2007
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