6 results on '"Puxeddu, Efisio"'
Search Results
2. BRAF V600E Mutation-Assisted Risk Stratification of Solitary Intrathyroidal Papillary Thyroid Cancer for Precision Treatment.
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Huang, Yueye, Qu, Shen, Zhu, Guangwu, Wang, Fei, Liu, Rengyun, Shen, Xiaopei, Viola, David, Elisei, Rossella, Puxeddu, Efisio, Fugazzola, Laura, Colombo, Carla, Jarzab, Barbara, Czarniecka, Agnieszka, Lam, Alfred K, Mian, Caterina, Vianello, Federica, Yip, Linwah, Riesco-Eizaguirre, Garcilaso, Santisteban, Pilar, and O'Neill, Christine J
- Abstract
Background: Precise risk stratification-based treatment of solitary intrathyroidal papillary thyroid cancer (SI-PTC) that is larger than 1.0 cm and 4.0 cm or less is undefined.Methods: A genetic-clinical risk study was performed on BRAF V600E in 955 patients (768 women and 187 men) with SI-PTC, with median age of 46 years and median clinical follow-up time of 64 months at 11 medical centers in six countries. The chi-square test or, for analyses with small numbers, Fisher's exact test was performed to compare recurrence rates. Recurrence-free probability was estimated by Kaplan-Meier (KM) analysis, and the independent effect of BRAF mutation on the recurrence was analyzed by Cox regression and Cox proportional hazard analyses. All statistical tests were two-sided.Results: Recurrence of SI-PTC larger than 1.0 cm and 4.0 cm or less was 9.5% (21/221) vs 3.4% (11/319) in BRAF mutation vs wild-type BRAF patients, with a hazard ratio (HR) of 3.03 (95% confidence interval [CI] = 1.46 to 6.30) and a patient age- and sex-adjusted hazard ratio of 3.10 (95% CI = 1.49 to 6.45, P = .002). Recurrence rates of SI-PTC larger than 2.0 cm and 4.0 cm or less were 16.5% (13/79) vs 3.6% (5/139) in mutation vs wild-type patients (HR = 5.44, 95% CI = 1.93 to 15.34; and adjusted HR = 5.58, 95% CI = 1.96 to 15.85, P = .001). Recurrence rates of SI-PTC larger than 3.0 cm and 4 cm or less were 30.0% (6/20) vs 1.9% (1/54) in mutation vs wild-type patients (HR = 18.40, 95% CI = 2.21 to 152.98; and adjusted HR = 14.73, 95% CI = 1.74 to 124.80, P = .01). Recurrences of mutation-positive SI-PTC were comparable with those of counterpart invasive solitary PTC, around 20% to 30%, in tumors larger than 2.0 cm to 3.0 cm. BRAF mutation was associated with a statistically significant decrease in recurrence-free patient survival on KM analysis, particularly in SI-PTC larger than 2.0 cm and 4.0 cm or less. Similar results were obtained in conventional SI-PTC. The negative predictive values of BRAF mutation for recurrence were 97.8% (95% CI = 96.3% to 98.8%) for general SI-PTC and 98.2% (95% CI = 96.3% to 99.3%) for conventional SI-PTC.Conclusions: BRAF V600E identifies a subgroup of SI-PTC larger than 1.0 cm and 4.0 cm or less, particularly tumors larger than 2.0 cm and 4.0 cm or less, that has high risk for recurrence comparable with that of invasive solitary PTC, making more aggressive treatment reasonable. [ABSTRACT FROM AUTHOR]- Published
- 2018
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3. Isozyme-specific abnormalities of PKC in thyroid cancer: evidence for post-transcriptional changes in PKC epsilon
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Knauf, J. A., Ward, L. S., Nikiforov, Y. E., Nikiforova, M., Puxeddu, Efisio, Medvedovic, M., Liron, T., and Fagin, J. A.
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Thyroid carcinoma ,PKC epsilon - Published
- 2002
4. Intracellular signal transduction and modification of the tumor microenvironment induced by RET/PTCs in papillary thyroid carcinoma.
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Menicali, Elisa, Moretti, Sonia, Voce, Pasquale, Romagnoli, Serena, Avenia, Nicola, Puxeddu, Efisio, Nucera, Carmelo, Pierotti, Marco Alessandro, and Soares, Paula
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CELLULAR signal transduction ,GENE rearrangement ,GENETIC mutation ,THYROID cancer ,ONCOGENES - Abstract
RET gene rearrangements (RET/PTCs) represent together with BRAF point mutations the two major groups of mutations involved in papillary thyroid carcinoma (PTC) initiation and progression. In this review, we will examine the mechanisms involved in RET/PTC-induced thyroid cell transformation. In detail, we will summarize the data on the molecular mechanisms involved in RET/PTC formation and in its function as a dominant oncogene, on the activated signal transduction pathways and on the induced gene expression modifications. Moreover, we will report on the effects of RET/PTCs on the tumor microenvironment. Finally, a short review of the literature on RET/PTC prognostic significance will be presented. [ABSTRACT FROM AUTHOR]
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- 2012
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5. Minimal Extrathyroidal Extension in Predicting 1-Year Outcomes: A Longitudinal Multicenter Study of Low-to-Intermediate-Risk Papillary Thyroid Carcinoma (ITCO#4)
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Barbara Puligheddu, Loredana Pagano, Sebastiano Filetti, Giovanni Tallini, Giovanna Spiazzi, Andrea Repaci, Valentina Zilioli, Giorgio Grani, Silvia Morelli, Umberto Ferraro Petrillo, Dario Tumino, Luciano Pezzullo, Alberto Ragni, Efisio Puxeddu, Marco Alfò, Marco Centanni, Laura Fugazzola, R. Rossetto, Maria Grazia Castagna, Raffaele Giubbini, Clotilde Sparano, Anna Crescenzi, Raffaella Forleo, Massimo Torlontano, Celestino Pio Lombardi, Maurilio Deandrea, Alessandro Piovesan, Cosimo Durante, Fabio Monzani, Alessandro Antonelli, Rocco Bruno, Salvatore Monti, Maria Chiara Zatelli, Irene Gagliardi, Graziano Ceresini, Forleo, Raffaella, Grani, Giorgio, Alfò, Marco, Zilioli, Valentina, Giubbini, Raffaele, Zatelli, Maria Chiara, Gagliardi, Irene, Piovesan, Alessandro, Ragni, Alberto, Morelli, Silvia, Puxeddu, Efisio, Pagano, Loredana, Deandrea, Maurilio, Ceresini, Graziano, Torlontano, Massimo, Puligheddu, Barbara, Antonelli, Alessandro, Centanni, Marco, Fugazzola, Laura, Spiazzi, Giovanna, Monti, Salvatore, Rossetto, Ruth, Monzani, Fabio, Tallini, Giovanni, Crescenzi, Anna, Sparano, Clotilde, Bruno, Rocco, Repaci, Andrea, Tumino, Dario, Pezzullo, Luciano, Lombardi, Celestino Pio, Ferraro Petrillo, Umberto, Filetti, Sebastiano, Durante, Cosimo, and Castagna, Maria Grazia
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extrathyroidal extension ,Oncology ,Adult ,Male ,medicine.medical_specialty ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,MEDLINE ,Papillary thyroid carcinoma ,Radioactive iodine remnant ablation ,Thyroid carcinoma ,Iodine Radioisotopes ,Endocrinology ,Internal medicine ,medicine ,Humans ,Longitudinal Studies ,Prospective Studies ,Thyroid Neoplasms ,Risk factor ,aggressive histology ,Tumor size ,business.industry ,micropapillary thyroid cancer ,Middle Aged ,PTC ,Multicenter study ,Thyroid Cancer, Papillary ,aggressive histology, micropapillary thyroid cancer, minimal extrathyroidal extension, PTC, tumor diameter ,Thyroidectomy ,Female ,tumor diameter ,minimal extrathyroidal extension ,business ,Intermediate risk - Abstract
Background: The role of minimal extrathyroidal extension (mETE) as a risk factor for persistent papillary thyroid carcinoma (PTC) is still debated. The aim of this study was to assess the clinical impact of mETE as a predictor of worse initial treatment response in PTC patients and to verify the impact of radioiodine therapy after surgery in patients with mETE. Methods: We reviewed all records in the Italian Thyroid Cancer Observatory (ITCO) database and selected 2237 consecutive patients with PTC who satisfied the inclusion criteria (PTC with no lymph node metastases and at least 1 year of follow-up). For each case, we considered initial surgery, histological variant of PTC, tumor diameter, recurrence risk class according to the American Thyroid Association (ATA) risk stratification system, use of radioiodine therapy, and initial therapy response, as suggested by ATA guidelines. Results: At 1-year follow-up, 1831 patients (81.8%) had an excellent response, 296 (13.2%) had an indeterminate response, 55 (2.5%) had a biochemical incomplete response, and 55 (2.5%) had a structural incomplete response. Statistical analysis suggested that mETE (odds ratio [OR] 1.16, p=0.65), tumor size >2 cm (OR 1.45, p=0.34), aggressive PTC histology (OR 0.55, p=0.15), and age at diagnosis (OR 0.90, p=0.32) were not significant risk factors for a worse initial therapy response. When evaluating the combination of mETE, tumor size, and aggressive PTC histology, the presence of mETE with a >2 cm tumor was significantly associated with a worse outcome (OR 5.27, 95% CI, p=0.014). The role of radioiodine ablation in patients with mETE was also evaluated. When considering radioiodine treatment, propensity score-based matching was performed, and no significant differences were found between treated and non-treated patients (p=0.24). Conclusions: This study failed to show the prognostic value of mETE in predicting initial therapy response in a large cohort of PTC patients without lymph node metastases. The study suggests that the combination of tumor diameter and mETE can be used as a reliable prognostic factor for persistence and could be easily applied in clinical practice to manage PTC patients with low-to-intermediate risk of recurrent/persistent disease.
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- 2021
6. Differential Clinicopathological Risk and Prognosis of Major Papillary Thyroid Cancer Variants
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Rossella Elisei, Manuel Sobrinho-Simões, Shen Qu, Xiaoguang Shi, Pilar Santisteban, Mark Sywak, Zhongyan Shan, Qing Wei, Giovanni Tallini, Rengyun Liu, Khawla S. Al-Kuraya, Sylvia L. Asa, Sonia Cheng, Roderick J. Clifton-Bligh, Alfred King-Yin Lam, Barbara Jarzab, Federica Vianello, Yangang Wang, Elizabeth H. Holt, Laura Fugazzola, Paula Soares, Carla Colombo, Caterina Mian, Hongyu Yu, Vlasta Sykorova, Haixia Guan, Shihua Zhao, Thomas J. Musholt, Xiaopei Shen, Tae Yong Kim, Vasily Vasko, Bela Bendlova, Linwah Yip, Garcilaso Riesco-Eizaguirre, Electron Kebebew, Weiping Teng, Janete M. Cerutti, Di Teng, Huixiong Xu, Mingzhao Xing, Gisele Oler, Young Kee Shong, Efisio Puxeddu, Christine J. O'Neill, Agnieszka Czarniecka, Riccardo Giannini, David Viola, Fulvio Basolo, Shi, Xiaoguang, Liu, Rengyun, Basolo, Fulvio, Giannini, Riccardo, Shen, Xiaopei, Teng, Di, Guan, Haixia, Shan, Zhongyan, Teng, Weiping, Musholt, Thomas J, Al-Kuraya, Khawla, Fugazzola, Laura, Colombo, Carla, Kebebew, Electron, Jarzab, Barbara, Czarniecka, Agnieszka, Bendlova, Bela, Sykorova, Vlasta, Sobrinho-Simões, Manuel, Soares, Paula, Kee Shong, Young, Yong Kim, Tae, Cheng, Sonia, Asa, Sylvia L, Viola, David, Elisei, Rossella, Yip, Linwah, Mian, Caterina, Vianello, Federica, Wang, Yangang, Zhao, Shihua, Oler, Gisele, Cerutti, Janete M, Puxeddu, Efisio, Qu, Shen, Wei, Qing, Xu, Huixiong, O'Neill, Christine J, Sywak, Mark S, Clifton-Bligh, Roderick, Lam, Alfred K, Riesco-Eizaguirre, Garcilaso, Santisteban, Pilar, Yu, Hongyu, Tallini, Giovanni, Holt, Elizabeth H, Vasko, Vasily, Xing, Mingzhao, National Institutes of Health (US), National Science Centre (Poland), Queensland Government, Griffith University, Instituto de Salud Carlos III, Comunidad de Madrid, Fondazione Cassa di Risparmio di Perugia, Associazione Italiana per la Ricerca sul Cancro, Beadle Family Foundation, Ministry of Health of the Czech Republic, Cancer Institute NSW (Australia), Cancer Council NSW (Australia), Ministero della Salute, Ministero dell'Istruzione, dell'Università e della Ricerca, Istituto Toscano Tumori, Korean Foundation for Cancer Research, Sao Paulo Research Foundation, Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brasil), Shanghai Jiao Tong University, Quadro de Referência Estratégico Nacional (Portugal), and European Commission
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Male ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Papillary ,Adult ,Carcinoma ,Carcinoma, Papillary ,Cohort Studies ,Female ,Follow-Up Studies ,Gene Frequency ,Humans ,Middle Aged ,Neoplasm Metastasis ,Prevalence ,Prognosis ,Radiotherapy ,Retrospective Studies ,Risk Assessment ,Thyroid Cancer, Papillary ,Thyroid Neoplasms ,Neoplasm Recurrence, Local ,Thyroid Cancer ,Biochemistry ,Papillary thyroid cancer ,Thyroid carcinoma, Papillary Thyroid Carcinoma Variants, Prognosis ,0302 clinical medicine ,Endocrinology ,Interquartile range ,Diabetes and Metabolism ,Local ,030220 oncology & carcinogenesis ,Cohort study ,medicine.medical_specialty ,Biochemistry (medical) ,030209 endocrinology & metabolism ,Context (language use) ,Thyroid carcinoma ,03 medical and health sciences ,Internal medicine ,medicine ,business.industry ,Cancer ,Retrospective cohort study ,Original Articles ,medicine.disease ,Neoplasm Recurrence ,business - Abstract
et al., [Context]: Individualized management, incorporating papillary thyroid cancer (PTC) variant-specific risk, is conceivably a useful treatment strategy for PTC, which awaits comprehensive data demonstrating differential risks of PTC variants to support. [Objective]: This study sought to establish the differential clinicopathological risk of major PTC variants: conventional PTC (CPTC), follicular-variant PTC (FVPTC), and tall-cell PTC (TCPTC). [Methods]: This was a retrospective study of clinicopathological outcomes of 6282 PTC patients (4799 females and 1483 males) from 26 centers and The Cancer Genome Atlas in 14 countries with a median age of 44 years (interquartile range, 33-56 y) and median follow-up time of 37 months (interquartile range, 15-82 mo)., [Results]: The cohort consisted of 4702 (74.8%) patients with CPTC, 1126 (17.9%) with FVPTC, and 239 (3.8%) with TCPTC. The prevalence of high-risk parameters was significantly different among the three variants, including extrathyroidal invasion, lymph node metastasis, stages III/IV, disease recurrence, mortality, and the use (need) of radioiodine treatment (all P < .001), being highest in TCPTC, lowest in FVPTC, and intermediate in CPTC, following an order of TCPTC > CPTC ≫ FVPTC. Recurrence and mortality in TCPTC, CPTC, and FVPTC were 27.3 and 6.7%, 16.1 and 2.5%, and 9.1 and 0.6%, corresponding to events per 1000 person-years (95% confidence interval [CI]) of 92.47 (64.66-132.26) and 24.61 (12.31-49.21), 34.46 (30.71-38.66), and 5.87 (4.37-7.88), and 24.73 (18.34-33.35) and 1.68 (0.54-5.21), respectively. Mortality hazard ratios of CPTC and TCPTC over FVPTC were 3.44 (95% CI, 1.07-11.11) and 14.96 (95% CI, 3.93-56.89), respectively. Kaplan-Meier survival analyses showed the best prognosis in FVPTC, worst in TCPTC, and intermediate in CPTC in disease recurrence-free probability and disease-specific patient survival. This was particularly the case in patients at least 45 years old. [Conclusion]: This large multicenter study demonstrates differential prognostic risks of the three major PTC variants and establishes a unique risk order of TCPTC > CPTC ≫ FVPTC, providing important clinical implications for specific variant-based management of PTC., This work was supported by the US National Institutes of Health (NIH) Grants No. RO1CA113507 and R01CA189224 (to M.X.). In addition, the studies at individual centers were supported as follows: National Science Centre Poland Grants No. N403 194340 and N N401 612440 to A.C. and B.J., respectively, and Milestone Grant No. 267398 to both (Poland); Grants from Queensland Government Smart State Fellowship and Griffith Health Institute to A.K.L. (Australia); Grants No. RD12/0036/0030 FIS-ISCIII, S2011/BMD-2328 TIRONET, and SAF2013-44709-R to P.So. (Spain); grants from Fondazione Cassa di Risparmio di Perugia and Associazione Italiana per la Ricerca sul Cancro (IG 9338) (Italy) and the Beadle Family Foundation (San Antonio, TX) to E.P.; Grant IGA MH CR NT 13901-4 to V.S. and B.B. (the Czech Republic); grants from the New South Wales Cancer Institute to C.J.O. and from Cancer Council of New South Wales to R.C.-B. (Australia); Italian Government-Ministero della Salute Grant No. RF-2011-02350857 to G.T. (Italy); Grant NIH/NIA 5R03AG042334-02 to L.Y. (United States); Grants from the Ministerodella Istruzione Universitaria e Ricerca Scientifica, the AssociazioneItaliana per la Ricerca sul Cancro, the Istituto Toscano Tumori, and the Ministero della Salute to D.V. and R.E (Italy); and Grant No. CB-2011-03-02 from the Korean Foundation for Cancer Research to Y.K.S. and T.Y.K. (South Korea); Research Grants 2012/02902-9 and 2013/03867-5 from The São Paulo State Research Foundation (FAPESP) to J.M.C. (G.O. is a FAPESP scholar and J.M.C. is a Brazilian Research Council investigator (Brazil); AIRC Grant No. IG 10316 to F.B. (Italy); Grant No. SHDC 12014229 from Shanghai Hospital Development Center to H.X. (China); Programa Operacional Regional do Norte (ON.2—O Novo Norte), under the Quadro de Referência Estratégico Nacional, and through the Fundo Europeu de Desenvolvimento Regional to M.S.-S. and P.So.
- Published
- 2016
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