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Association between BRAFV600E and NRASQ61R mutations and clinicopathologic characteristics, risk factors and clinical outcome of primary invasive cutaneous melanoma.

ABSTRACT: Previous studies suggest that solar UV exposure in early life is predictive of cutaneous melanoma risk in adulthood, whereas the relation of BRAF mutation with sun exposure and disease prognosis has been less certain. We investigated the associations between BRAF(V600E) and NRAS(Q61R) mutations and known risk factors, clinicopathologic characteristics and clinical outcomes of melanoma in a case series of primary invasive cutaneous melanoma from the Nurses' Health Study (NHS).Somatic BRAF(V600E) and NRAS(Q61R) mutations of 127 primary invasive melanomas from the NHS cohort were determined by pyrosequencing using formalin-fixed, paraffin-embedded block tissues. Logistic regression analyses were performed to detect the associations of mutations with melanoma risk factors, and Kaplan-Meier method was used to examine associations between mutations and survival.The odds ratios for harboring BRAF(V600E) mutations were 5.54 (95% CI 1.19-25.8, p(trend) = 0.02) for women residing in states with UV index ? 7 versus those residing in states with UV index ?5 at 30 years of age. Patients with BRAF(V600E) mutations tended to have shorter melanoma-specific survival when compared to patients with wild type at both loci (median survival time 110 vs. 159 months) (p = 0.03). No association was found between NRASQ61R mutation and melanoma risk factors or melanoma-specific survival.BRAF(V600E) mutations in primary cutaneous melanomas were associated with residence in locations with medium and high UV indices in mid-life. BRAF(V600E) mutation may be associated with an unfavorable prognosis among melanoma patients.

SUBMITTER: Wu S

PROVIDER: S-EPMC4220546 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Association between BRAFV600E and NRASQ61R mutations and clinicopathologic characteristics, risk factors and clinical outcome of primary invasive cutaneous melanoma.

Wu Shaowei S Kuo Helen H Li Wen-Qing WQ Canales Alvaro Laga AL Han Jiali J Qureshi Abrar A AA

Cancer causes & control : CCC 20140722 10

<h4>Purpose</h4>Previous studies suggest that solar UV exposure in early life is predictive of cutaneous melanoma risk in adulthood, whereas the relation of BRAF mutation with sun exposure and disease prognosis has been less certain. We investigated the associations between BRAF(V600E) and NRAS(Q61R) mutations and known risk factors, clinicopathologic characteristics and clinical outcomes of melanoma in a case series of primary invasive cutaneous melanoma from the Nurses' Health Study (NHS).<h4> ...[more]

PMID: 25048604

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Project description:PURPOSE:Lung cancer in never smokers is recognized as a distinct molecular, clinicopathologic and epidemiologic entity. The aim of the study was to investigate the molecular profile in Swiss never smokers with lung adenocarcinoma and to correlate the mutation status with clinicopathologic and demographic patient characteristics and outcome. METHODS:One hundred thirty-eight never smokers diagnosed with lung adenocarcinoma at the University Hospital Zurich between 2011-2018 were included in the study. Data from the electronic medical records were reviewed to characterize clinicopathologic and demographic features, molecular profile, treatment and outcome. RESULTS:The majority of patients were female (58.7%) with a median age at diagnosis of 64.5 years (range, 27.1-94.2 years). The most common mutations were EGFR (58.7%) followed by ALK (12.3%), TP53 (5.8%), MET (5.8%), KRAS (4.3%), ERBB2 (4.3%), PIK3CA (2.9%), BRAF (2.2%), ROS1 (1.4%), RET (1.4%), CTNNB1 (0.7%), PARP1 (0.7%), TET1 (0.7%) and PIK3CG (0.7%). Median overall survival (mOS) was 51.0 months (mo). Early clinical stage (p = 0.002) and treatment with targeted therapy (HR 2.53, 95% CI 1.35-4.74, p = 0.004) were independently associated with longer mOS. Patients with oncogenic driver mutations had significantly longer mOS (52.2 mo) compared to patients without mutations (16.9 mo) (HR 3.38, 95% CI 1.52-7.55, p = 0.003). Besides, patients with EGFR mutated (57.8 mo) or ALK rearranged (59.9 mo) tumors had significantly longer mOS compared to the EGFR wildtype (35.0 mo), ALK wildtype (46.5 mo) and pan-negative (16.9 mo) cohorts (HR 2.35, 95% CI 1.37-4.04, p = 0.002; HR 7.80, 95% CI 3.28-18.55, p < 0.001; HR 3.96, 95% CI 1.21-12.95, p = 0.023 and HR 34.78, 95% CI 3.48-34.65, p = 0.003). CONCLUSION:Never smokers with lung adenocarcinoma display distinct clinicopathologic and molecular features and are characterized by a high incidence of targetable mutations. Never smokers with targetable mutations have significantly longer survival compared to patients without mutations.

Project description:BackgroundSimultaneous multiple primary lung cancer has been detected increasingly nowadays with the development of image technology. However, the clinicopathologic characteristics and outcomes are not clear.MethodsAll consecutive patients diagnosed as simultaneous multiple primary lung cancer according to Martini-Melamed and American College of Chest Physicians criteria from June 2010 to June 2019 in our center were enrolled. The clinicopathologic characteristics and outcomes were compared between patients with the same histological type and different histological types.ResultsA total of 336 patients were enrolled, consisting of 297 (88.4%) patients with the same histological type and 39 (11.6%) patients with different histological types. Compared to patients with the same histological type, patients with different histological types were more commonly males (87.2% vs. 34.0%; p < 0.001) with an older age (65 [62-69] vs. 59 [52-65] yrs; p < 0.001) at diagnosis. Also, patients with different histological types showed worse respiratory function and more advanced stage according to TNM staging. The 1-, 2-, and 3-year overall survival of overall patients was 97.7%, 96.1%, and 92.2%, and the 1-, 2-, and 3-year recurrence-free survival of overall patients was 96.8%, 92.9% and 85.7%, respectively. Importantly, patients with different histological types showed worse overall survival (p < 0.001) and recurrence-free survival (p=0.002) than patients with same histological type. The multivariable Cox proportional hazard model revealed that presence of different histological types was significant predictor for worse overall survival (adjusted hazard ratio: 10.00; 95% confidence interval: 2.92-34.48; p < 0.001) and recurrence-free survival (adjusted hazard ratio: 2.59; 95% confidence interval: 1.14-5.88; p=0.023).ConclusionsAlthough relatively less common in simultaneous multiple primary lung cancer, patients with different histological types showed worse clinical characteristics and outcomes.

Dataset Information

Association between BRAFV600E and NRASQ61R mutations and clinicopathologic characteristics, risk factors and clinical outcome of primary invasive cutaneous melanoma.

Publications

Association between BRAFV600E and NRASQ61R mutations and clinicopathologic characteristics, risk factors and clinical outcome of primary invasive cutaneous melanoma.

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