BRAF V600E Status Sharply Differentiates Lymph Node Metastasis-associated Mortality Risk in Papillary Thyroid Cancer
Language English Country United States Media print
Document type Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
Grant support
5R03AG042334-02
NIH HHS - United States
R03 AG042334
NIA NIH HHS - United States
PubMed
34273152
PubMed Central
PMC8530728
DOI
10.1210/clinem/dgab286
PII: 6323355
Knihovny.cz E-resources
- Keywords
- BRAF mutation, lymph node metastasis, mortality, prognostic molecular marker, risk stratification, thyroid cancer,
- MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Neoplasm Recurrence, Local genetics mortality pathology MeSH
- Lymphatic Metastasis MeSH
- Survival Rate MeSH
- Mutation * MeSH
- Biomarkers, Tumor genetics MeSH
- Thyroid Neoplasms genetics mortality pathology MeSH
- Follow-Up Studies MeSH
- Thyroid Cancer, Papillary genetics mortality secondary MeSH
- Prognosis MeSH
- Proto-Oncogene Proteins B-raf genetics MeSH
- Retrospective Studies MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
- Names of Substances
- BRAF protein, human MeSH Browser
- Biomarkers, Tumor MeSH
- Proto-Oncogene Proteins B-raf MeSH
CONTEXT: How lymph node metastasis (LNM)-associated mortality risk is affected by BRAF V600E in papillary thyroid cancer (PTC) remains undefined. OBJECTIVE: To study whether BRAF V600E affected LNM-associated mortality in PTC. DESIGN, SETTING, AND PARTICIPANTS: 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. RESULTS: 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. CONCLUSIONS: 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.
Cancer Molecular Pathology of School of Medicine Griffith University Gold Coast Australia
Ciberonc Health Institute Carlos 3 Madrid Spain
Department of Medicine Endocrinology Unit University of Padua Padua Italy
Department of Medicine University of Perugia Perugia Italy
Department of Molecular Endocrinology Institute of Endocrinology Prague Czech Republic
Endocrine Surgical Unit University of Sydney Sydney Australia
Endocrine Unit Department of Clinical and Experimental Medicine University of Pisa Pisa Italy
Maria Sklodowska Curie National Institute of Oncology Gliwice Branch Gliwice Poland
University of Pittsburgh School of Medicine Pittsburgh PA USA
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