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, Shong Young Kee, Kim Tae Yong, 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
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 Meta
J Clin Endocrinol Metab. 2016 Jan;101(1):264-74. doi: 10.1210/jc.2015-2917. Epub 2015 Nov 3.
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.
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).
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).
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.
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.
将甲状腺乳头状癌（PTC）变异体特异性风险纳入其中的个体化管理，理论上是一种对PTC有用的治疗策略，但尚需全面数据来证明PTC变异体的不同风险以提供支持。
本研究旨在确定主要PTC变异体的不同临床病理风险：传统型PTC（CPTC）、滤泡型变异体PTC（FVPTC）和高细胞型PTC（TCPTC）。
这是一项对来自26个中心和14个国家的癌症基因组图谱的6282例PTC患者（4799例女性和1483例男性）的临床病理结果进行的回顾性研究，患者中位年龄为44岁（四分位间距，33 - 56岁），中位随访时间为37个月（四分位间距，15 - 82个月）。
该队列包括4702例（74.8%）CPTC患者、1126例（17.9%）FVPTC患者和239例（3.8%）TCPTC患者。三种变异体中高危参数的发生率存在显著差异，包括甲状腺外侵犯、淋巴结转移、III/IV期、疾病复发、死亡率以及放射性碘治疗的使用（需求）（所有P < 0.001），在TCPTC中最高，在FVPTC中最低，在CPTC中居中，顺序为TCPTC > CPTC ≫ FVPTC。TCPTC、CPTC和FVPTC的复发率和死亡率分别为27.3%和6.7%、16.1%和2.5%、9.1%和0.6%，相当于每1000人年的事件数（95%置信区间[CI]）分别为92.47（64.66 - 132.26）和24.61（12.31 - 49.21）、34.46（30.71 - 38.66）和5.87（4.37 - 7.88）、24.73（18.34 - 33.35）和1.68（0.54 - 5.21）。CPTC和TCPTC相对于FVPTC的死亡风险比分别为3.44（95% CI，1.07 - 11.11）和14.96（95% CI，3.93 - 56.89）。Kaplan - Meier生存分析显示在无疾病复发概率和疾病特异性患者生存方面，FVPTC预后最佳，TCPTC最差，CPTC居中。至少45岁的患者尤其如此。
这项大型多中心研究证明了三种主要PTC变异体的不同预后风险，并确立了独特的风险顺序TCPTC > CPTC ≫ FVPTC，为基于特定变异体的PTC管理提供了重要的临床意义。
