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- Title
BRAF V600E Status Sharply Differentiates Lymph Node Metastasis-associated Mortality Risk in Papillary Thyroid Cancer.
- Authors
Yubing Tao; Fei Wang; Xiaopei Shen; Guangwu Zhu; Rengyun Liu; 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; O'Neill, Christine J.; Sywak, Mark S.
- Abstract
<bold>Context: </bold>How lymph node metastasis (LNM)-associated mortality risk is affected by BRAF V600E in papillary thyroid cancer (PTC) remains undefined.<bold>Objective: </bold>To study whether BRAF V600E affected LNM-associated mortality in PTC.<bold>Design, Setting, and Participants: </bold>We retrospectively analyzed the effect of LNM on PTC-specific mortality with respect to BRAF status in 2638 patients (2015 females and 623 males) from 11 centers in 6 countries, with median age of 46 [interquartile range (IQR) 35-58] years and median follow-up time of 58 (IQR 26-107) months.<bold>Results: </bold>Overall, LNM showed a modest mortality risk in wild-type BRAF patients but a strong one in BRAF V600E patients. In conventional PTC (CPTC), LNM showed no increased mortality risk in wild-type BRAF patients but a robustly increased one in BRAF V600E patients; mortality rates were 2/659 (0.3%) vs 4/321 (1.2%) in non-LNM vs LNM patients (P = 0.094) with wild-type BRAF, corresponding to a hazard ratio (HR) (95% CI) of 4.37 (0.80-23.89), which remained insignificant at 3.32 (0.52-21.14) after multivariate adjustment. In BRAF V600E CPTC, morality rates were 7/515 (1.4%) vs 28/363 (7.7%) in non-LNM vs LNM patients (P < 0.001), corresponding to an HR of 4.90 (2.12-11.29) or, after multivariate adjustment, 5.76 (2.19-15.11). Adjusted mortality HR of coexisting LNM and BRAF V600E vs absence of both was 27.39 (5.15-145.80), with Kaplan-Meier analyses showing a similar synergism.<bold>Conclusions: </bold>LNM-associated mortality risk is sharply differentiated by the BRAF status in PTC; in CPTC, LNM showed no increased mortality risk with wild-type BRAF but a robust one with BRAF mutation. These results have strong clinical relevance.
- Subjects
BRAF genes; LYMPH node diseases; THYROID cancer; RESEARCH; GENETIC mutation; THYROID gland tumors; RESEARCH methodology; CANCER relapse; METASTASIS; RETROSPECTIVE studies; PROGNOSIS; MEDICAL cooperation; EVALUATION research; COMPARATIVE studies; TRANSFERASES; RESEARCH funding; LONGITUDINAL method
- Publication
Journal of Clinical Endocrinology & Metabolism, 2021, Vol 106, Issue 11, p3228
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/clinem/dgab286