Association of the Genomic Profile of Medullary Thyroid Carcinoma with Tumor Characteristics and Clinical Outcomes in an International Multicenter Study.

Autor: Xu B; Department of Pathology and Laboratory Medicine; New York, New York, USA., Viswanathan K; Department of Pathology, Emory University Hospital Midtown, Atlanta, Georgia, USA., Ahadi MS; Royal North Shore Hospital and Northern Clinical School, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.; Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research; Department of Anatomical Pathology; Royal North Shore Hospital, St Leonards, New South Wales, Australia.; NSW Health Pathology, Department of Anatomical Pathology; Royal North Shore Hospital, St Leonards, New South Wales, Australia., Ahmadi S; Division of Endocrinology and Metabolism, Department of Medicine; Boston, Harvard Medical School, Boston, Massachusetts, USA., Alzumaili B; Department of Pathology and Laboratory Medicine; New York, New York, USA., Bani MA; Medical Pathology and Biology Department; Service d'oncologie endocrinienne; Gustave Roussy Campus Cancer, Villejuif, France., Baudin E; Département d'imagerie, Service d'oncologie endocrinienne; Gustave Roussy Campus Cancer, Villejuif, France., Behrman DB; Department of Pathology, Emory University Hospital Midtown, Atlanta, Georgia, USA., Capelletti M; Department of Pathology; Brigham and Women's Hospital, Boston, Harvard Medical School, Boston, Massachusetts, USA., Chau NG; Department of Pathology; Brigham and Women's Hospital, Boston, Harvard Medical School, Boston, Massachusetts, USA., Chiarucci F; Department of Medical and Surgical Sciences (DIMEC), University of Bologna Medical Center; Bologna, Italy., Chou A; Royal North Shore Hospital and Northern Clinical School, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.; Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research; Department of Anatomical Pathology; Royal North Shore Hospital, St Leonards, New South Wales, Australia.; NSW Health Pathology, Department of Anatomical Pathology; Royal North Shore Hospital, St Leonards, New South Wales, Australia., Clifton-Bligh R; Royal North Shore Hospital and Northern Clinical School, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.; Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research; Department of Anatomical Pathology; Royal North Shore Hospital, St Leonards, New South Wales, Australia.; NSW Health Pathology, Department of Anatomical Pathology; Royal North Shore Hospital, St Leonards, New South Wales, Australia., Coluccelli S; Department of Medical and Surgical Sciences (DIMEC), University of Bologna Medical Center; Bologna, Italy., de Biase D; Department of Pharmacy and Biotechnology; Bologna, Italy., De Leo A; Department of Medical and Surgical Sciences (DIMEC), University of Bologna Medical Center; Bologna, Italy., Dogan S; Department of Pathology and Laboratory Medicine; New York, New York, USA., Fagin JA; Division of Specialized Medicine; New York, New York, USA., Fuchs TL; Royal North Shore Hospital and Northern Clinical School, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.; Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research; Department of Anatomical Pathology; Royal North Shore Hospital, St Leonards, New South Wales, Australia.; NSW Health Pathology, Department of Anatomical Pathology; Royal North Shore Hospital, St Leonards, New South Wales, Australia., Glover AR; Royal North Shore Hospital and Northern Clinical School, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia., Hadoux J; Département d'imagerie, Service d'oncologie endocrinienne; Gustave Roussy Campus Cancer, Villejuif, France., Lacroix L; Medical Pathology and Biology Department; Service d'oncologie endocrinienne; Gustave Roussy Campus Cancer, Villejuif, France., Lamartina L; Département d'imagerie, Service d'oncologie endocrinienne; Gustave Roussy Campus Cancer, Villejuif, France., Lubin DJ; Department of Pathology, Emory University Hospital Midtown, Atlanta, Georgia, USA., Luxford C; Royal North Shore Hospital and Northern Clinical School, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.; Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research; Department of Anatomical Pathology; Royal North Shore Hospital, St Leonards, New South Wales, Australia.; NSW Health Pathology, Department of Anatomical Pathology; Royal North Shore Hospital, St Leonards, New South Wales, Australia., Magliocca K; Department of Pathology, Emory University Hospital Midtown, Atlanta, Georgia, USA., Maloberti T; Department of Medical and Surgical Sciences (DIMEC), University of Bologna Medical Center; Bologna, Italy., Mohanty AS; Department of Pathology and Laboratory Medicine; New York, New York, USA., Najdawi F; Department of Pathology; Brigham and Women's Hospital, Boston, Harvard Medical School, Boston, Massachusetts, USA., Nigam A; Department of Surgery; Memorial Sloan Kettering Cancer Center, New York, New York, USA., Papachristos AJ; Royal North Shore Hospital and Northern Clinical School, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.; Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research; Department of Anatomical Pathology; Royal North Shore Hospital, St Leonards, New South Wales, Australia.; NSW Health Pathology, Department of Anatomical Pathology; Royal North Shore Hospital, St Leonards, New South Wales, Australia., Repaci A; Division of Endocrinology and Diabetes Prevention and Care; IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy., Robinson B; Royal North Shore Hospital and Northern Clinical School, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.; Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research; Department of Anatomical Pathology; Royal North Shore Hospital, St Leonards, New South Wales, Australia.; NSW Health Pathology, Department of Anatomical Pathology; Royal North Shore Hospital, St Leonards, New South Wales, Australia., Scoazec JY; Medical Pathology and Biology Department; Service d'oncologie endocrinienne; Gustave Roussy Campus Cancer, Villejuif, France., Shi Q; Department of Pathology, Emory University Hospital Midtown, Atlanta, Georgia, USA., Sidhu S; Royal North Shore Hospital and Northern Clinical School, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.; Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research; Department of Anatomical Pathology; Royal North Shore Hospital, St Leonards, New South Wales, Australia.; NSW Health Pathology, Department of Anatomical Pathology; Royal North Shore Hospital, St Leonards, New South Wales, Australia., Solaroli E; Endocrinology Unit, Azienda USL di Bologna, Bologna, Italy., Sywak M; Royal North Shore Hospital and Northern Clinical School, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.; Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research; Department of Anatomical Pathology; Royal North Shore Hospital, St Leonards, New South Wales, Australia.; NSW Health Pathology, Department of Anatomical Pathology; Royal North Shore Hospital, St Leonards, New South Wales, Australia., Tuttle RM; Division of Specialized Medicine; New York, New York, USA., Untch B; Department of Surgery; Memorial Sloan Kettering Cancer Center, New York, New York, USA., Barletta JA; Department of Pathology; Brigham and Women's Hospital, Boston, Harvard Medical School, Boston, Massachusetts, USA., Al Ghuzlan A; Medical Pathology and Biology Department; Service d'oncologie endocrinienne; Gustave Roussy Campus Cancer, Villejuif, France., Gill AJ; Royal North Shore Hospital and Northern Clinical School, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.; Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research; Department of Anatomical Pathology; Royal North Shore Hospital, St Leonards, New South Wales, Australia.; NSW Health Pathology, Department of Anatomical Pathology; Royal North Shore Hospital, St Leonards, New South Wales, Australia., Ghossein R; Department of Pathology and Laboratory Medicine; New York, New York, USA., Tallini G; Department of Medical and Surgical Sciences (DIMEC), University of Bologna Medical Center; Bologna, Italy., Ganly I; Department of Surgery; Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Jazyk: angličtina
Zdroj: Thyroid : official journal of the American Thyroid Association [Thyroid] 2024 Feb; Vol. 34 (2), pp. 167-176. Date of Electronic Publication: 2023 Nov 07.
DOI: 10.1089/thy.2023.0279
Abstrakt: Purpose: The prognostic importance of RET and RAS mutations and their relationship to clinicopathologic parameters and outcomes in medullary thyroid carcinoma (MTC) need to be clarified. Experimental Design: A multicenter retrospective cohort study was performed utilizing data from 290 patients with MTC. The molecular profile was determined and associations were examined with clinicopathologic data and outcomes. Results: RET germ line mutations were detected in 40 patients (16.3%). Somatic RET and RAS mutations occurred in 135 (46.9%) and 57 (19.8%) patients, respectively. RET M918T was the most common somatic RET mutation ( n  = 75). RET somatic mutations were associated with male sex, larger tumor size, advanced American Joint Committee Cancer (AJCC) stage, vascular invasion, and high International Medullary Thyroid Carcinoma Grading System (IMTCGS) grade. When compared with other RET somatic mutations, RET M918T was associated with younger age, AJCC (eighth edition) IV, vascular invasion, extrathyroidal extension, and positive margins. RET somatic or germ line mutations were significantly associated with reduced distant metastasis-free survival on univariate analysis, but there were no significant independent associations on multivariable analysis, after adjusting for tumor grade and stage. There were no significant differences in outcomes between RET somatic and RET germ line mutations, or between RET M918T and other RET mutations. Other recurrent molecular alterations included TP53 (4.2%), ARID2 (2.9%), SETD2 (2.9%), KMT2A (2.9%), and KMT2C (2.9%). Among them, TP53 mutations were associated with decreased overall survival (OS) and disease-specific survival (DSS), independently of tumor grade and AJCC stage. Conclusions: RET somatic mutations were associated with high-grade, aggressive primary tumor characteristics, and decreased distant metastatic-free survival but this relationship was not significant after accounting for tumor grade and disease stage. RET M918T was associated with aggressive primary tumors but was not independently associated with clinical outcomes. TP53 mutation may represent an adverse molecular event associated with decreased OS and DSS in MTC, but its prognostic value needs to be confirmed in future studies.
Databáze: MEDLINE