Association Between BRAF V600E Mutation and Recurrence of Papillary Thyroid Cancer

被引：466

作者：

Xing, Mingzhao ^{[1
]}

Alzahrani, Ali S. ^{[1
]}

Carson, Kathryn A. ^{[2
]}

Shong, Young Kee ^{[3
]}

Kim, Tae Yong ^{[3
]}

Viola, David ^{[4
]}

Elisei, Rossella ^{[4
]}

Bendlova, Bela ^{[11
]}

Yip, Linwah ^{[12
]}

Mian, Caterina ^{[5
]}

Vianello, Federica ^{[6
]}

Tuttle, R. Michael

Robenshtok, Eyal ^{[13
]}

Fagin, James A. ^{[13
]}

Puxeddu, Efisio ^{[7
]}

Fugazzola, Laura ^{[8
,9
]}

Czarniecka, Agnieszka ^{[14
,15
]}

Jarzab, Barbara ^{[14
,15
]}

O'Neill, Christine J. ^{[16
]}

Sywak, Mark S. ^{[16
]}

Lam, Alfred K. ^{[17
]}

Riesco-Eizaguirre, Garcilaso ^{[18
,19
,20
,21
]}

Santisteban, Pilar ^{[20
,21
]}

Nakayama, Hirotaka ^{[22
]}

Clifton-Bligh, Roderick ^{[16
]}

Tallini, Giovanni ^{[10
]}

Holt, Elizabeth H. ^{[23
]}

Sykorova, Vlasta ^{[11
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Baltimore, MD 21287 USA

[2] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21287 USA

[3] Univ Ulsan, Coll Med, Asan Med Ctr, Seoul, South Korea

[4] Univ Pisa, WHO Collaborating Ctr Study & Treatment Thyroid D, Pisa, Italy

[5] Univ Padua, Padua, Italy

[6] IRCCS, Veneto Inst Oncol, Padua, Italy

[7] Univ Perugia, I-06100 Perugia, Italy

[8] Univ Milan, Milan, Italy

[9] Fdn IRCCS CaGranda, Milan, Italy

[10] Univ Bologna, Bellaria Hosp, Sch Med, Bologna, Italy

[11] Inst Endocrinol, Prague, Czech Republic

[12] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA

[13] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA

[14] Maria Sklodowska Curie Mem Canc Ctr, Gliwice, Poland

[15] Inst Oncol, Gliwice, Poland

[16] Univ Sydney, Sydney, NSW 2006, Australia

[17] Griffith Univ, Sch Med, Gold Coast, Qld, Australia

[18] Hosp La Paz, Hlth Res Inst, Madrid, Spain

[19] Hosp Univ Mostoles, Madrid, Spain

[20] Spanish Council Res, Biomed Res Inst Alberto Sols, Madrid, Spain

[21] Autonomous Univ Madrid, E-28049 Madrid, Spain

[22] Kanagawa Canc Ctr, Yokohama, Kanagawa 2410815, Japan

[23] Yale Univ, Sch Med, New Haven, CT USA

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2015年 / 33卷 / 01期

基金：

美国国家卫生研究院;

关键词：

NEEDLE-ASPIRATION BIOPSY; BRAF(V600E) MUTATION; FOLLICULAR VARIANT; CARCINOMA; RISK; MANAGEMENT; PATHOGENESIS; COHORT;

D O I：

10.1200/JCO.2014.56.8253

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose To investigate the prognostic value of BRAF V600E mutation for the recurrence of papillary thyroid cancer (PTC). Patients and Methods This was a retrospective multicenter study of the relationship between BRAF V600E mutation and recurrence of PTC in 2,099 patients (1,615 women and 484 men), with a median age of 45 years (interquartile range [IQR], 34 to 58 years) and a median follow-up time of 36 months (IQR, 14 to 75 months). Results The overall BRAF V600E mutation prevalence was 48.5% (1,017 of 2,099). PTC recurrence occurred in 20.9% (213 of 1,017) of BRAF V600E mutation-positive and 11.6% (125 of 1,082) of BRAF V600E mutation-negative patients. Recurrence rates were 47.71 (95% CI, 41.72 to 54.57) versus 26.03 (95% CI, 21.85 to 31.02) per 1,000 person-years in BRAF mutation-positive versus -negative patients (P < .001), with a hazard ratio (HR) of 1.82 (95% CI, 1.46 to 2.28), which remained significant in a multivariable model adjusting for patient sex and age at diagnosis, medical center, and various conventional pathologic factors. Significant association between BRAF mutation and PTC recurrence was also found in patients with conventionally low-risk disease stage I or II and micro-PTC and within various subtypes of PTC. For example, in BRAF mutation-positive versus -negative follicular-variant PTC, recurrence occurred in 21.3% (19 of 89) and 7.0% (24 of 342) of patients, respectively, with recurrence rates of 53.84 (95% CI, 34.34 to 84.40) versus 19.47 (95% CI, 13.05 to 29.04) per 1,000 person-years (P < .001) and an HR of 3.20 (95% CI, 1.46 to 7.02) after adjustment for clinicopathologic factors. BRAF mutation was associated with poorer recurrence-free probability in Kaplan-Meier survival analyses in various clinicopathologic categories. Conclusion This large multicenter study demonstrates an independent prognostic value of BRAF V600E mutation for PTC recurrence in various clinicopathologic categories. (C) 2014 by American Society of Clinical Oncology

引用

页码：42 / U79

页数：13

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