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      Differential Clinicopathological Risk and Prognosis of Major Papillary Thyroid Cancer Variants

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      The Journal of Clinical Endocrinology and Metabolism
      Endocrine Society

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          Abstract

          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.

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          Author and article information

          Journal
          J Clin Endocrinol Metab
          J. Clin. Endocrinol. Metab
          jcem
          jceme
          jcem
          The Journal of Clinical Endocrinology and Metabolism
          Endocrine Society (Washington, DC )
          0021-972X
          1945-7197
          January 2016
          3 November 2015
          1 January 2017
          : 101
          : 1
          : 264-274
          Affiliations
          Laboratory for Cellular and Molecular Thyroid Research, Division of Endocrinology, Diabetes & Metabolism, Department of Medicine (X.Shi., R.L., X.Shen., D.T., M.X.), Johns Hopkins University School of Medicine, Baltimore, MD 21287; Department of Surgery, Division of Pathology (F.B., R.G.), 56126 Pisa, Italy; The Endocrine Institute and The Liaoning Provincial Key Laboratory of Endocrine Diseases, Department of Endocrinology and Metabolism (H.G., Z.S., W.T.), The First Hospital of China Medical University, Shenyang, Liaoning Province 110001, China; Endocrine Surgery (T.J.M.), University Medical Center, Johannes Gutenberg University Mainz, 55101 Mainz, Germany; Human Cancer Genomic Research (K.A.K.), Research Centre, King Faisal Specialist Hospital and Research Centre, Riyadh 12713, Kingdom of Saudi Arabia; Fondazione Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Policlinico, Milan, and Department of Pathophysiology and Transplantation (L.E., C.C.), University of Milan, 20122 Milan Italy; Endocrine Oncology Branch, Center for Cancer Research (E.K.), National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892; Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (A.C., B.J.), 44-101 Gliwice, Poland; Department of Molecular Endocrinology (B.B., V.S.), Institute of Endocrinology, Prague 11694, Czech Republic; Institute of Molecular Pathology and Immunology (Manuel Sobrinho-Simões, M.S.S.; Paula Soares, P.So.), University of Porto (Ipatimup) and Medical Faculty of the University of Porto, 4200-319 Porto, Portugal; College of Medicine (Y.K.S., T.Y.K.), University of Ulsan College of Medicine, Seoul, South Korea; Department of Pathology (S.C.; S.L.A.), University Health Network, Toronto, ON M5G 2C4 Canada; Endocrine Unit, Department of Clinical and Experimental Medicine (D.V., R.E.), World Health Organization, Collaborating Center for the Study and Treatment of Thyroid Diseases and Other Endocrine and Metabolic Disorders, University of Pisa, 56124 Pisa, Italy; University of Pittsburgh School of Medicine (L.Y.), Pittsburgh, Pennsylvania 15213; Department of Medicine, Endocrinology Unit (C.M.), University of Padua, Padua 35128, Italy; Veneto Institute of Oncology (F.V.), IRCCS, Padua 35128, Italy; Department of Endocrinology (Y.W., S.Z.), The Affiliated Hospital of Qingdao University, Qingdao 266003, China; Genetic Bases of Thyroid Tumor Laboratory, Division of Genetics (G.O., J.M.C.), Federal University of São Paulo, São Paulo 04039-032, Brazil; Department of Internal Medicine (E.P.), University of Perugia, 06100 Perugia, Italy; Department of Endocrinology (S.Q.), Department of Medical Ultrasound (H.X.), Shanghai Tenth People's Hospital, Thyroid Institute, Tongji University School of Medicine, Shanghai, 200072, China; Endocrine Surgical Unit (C.J.O., M.S.S., R.C.B.), The University of Sydney, Sydney 2052, Australia; Cancer Molecular Pathology of Menzies Health Institute Queensland (A.K.L.), Griffith University–Gold Coast, Southport 4215, Australia; Hospital La Paz, Health Research Institute, and Hospital Universitario de Móstoles (G.R.-E.), and Biomedical Research Institute (G.R.-E., P.Sa.), “Alberto Sols,” Spanish Council of Research Consejo Superior de Investigaciones Científicas, and Autonomous University of Madrid, Madrid, 28029 Madrid, Spain; Department of Pathology (H.Y.), Changzheng Hospital, Second Military Medical University, Shanghai 200003, China; Department of Medicine, Anatomic Pathology Unit (G.T.), Ospedale Bellaria, University of Bologna, 40139 Bologna, Italy; Endocrine Section, Department of Internal Medicine (E.H.H.), Yale University School of Medicine, New Haven, Connecticut 06520; and Department of Pediatrics (V.V.), Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814
          Author notes
          Address all correspondence and requests for reprints to: Michael Mingzhao Xing, MD, PhD, Division of Endocrinology, Diabetes & Metabolism, The Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 333, Baltimore, MD 21287. E-mail: mxing1@ 123456jhmi.edu .
          [*]

          X.Shi. and R.L. contributed equally to the study.

          Article
          PMC4701842 PMC4701842 4701842 15-2917
          10.1210/jc.2015-2917
          4701842
          26529630
          4a48decc-fc36-426d-984f-05b5d37c425c
          Copyright © 2016 by the Endocrine Society
          History
          : 18 July 2015
          : 29 October 2015
          Categories
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