Are BRAF V600E and K-Ras Mutations Associated With Tumor Aggressiveness in Well-Differentiated Thyroid Cancer?

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Aim: Many clinical studies have shown an association between B-type rapidly growing fibrosarcoma kinase [BRAF(V600E)] mutation and aggressive clinicopathologic features, although some results from others are controversial. Besides, Kirsten rat sarcoma (K-Ras) mutations are more common in endemic iodine deficiency regions, as our country is. However, use of the biologic markers are questioned in clinical practice; they are beginning to be used for the management of patients with thyroid nodules and cancers. The aim of the present study was to evaluate the prevalence of the BRAF(V600E) mutation in tumor samples and its relationship to high-risk clinicopathologic features. Methods: From 2000 to 2007, 82 patients with well-differentiated thyroid cancer (WDTC) who underwent surgery in Ege University were enrolled retrospectively in the study. Univariate and multivariate analyses were performed to analyze associations between BRAF(V600E) and K-Ras mutations and clinicopathologic features. We identified 82 patients with WDTC (male:female = 1:3.2). Results: The median follow-up was 96 months. The mean age was 46.4 (16–80). None of the all analyzed prognostic factors—age; sex; lymph node metastasis; multifocality; multicentricity; invasion; tumor diameter; and tumor, node, metastasis staging—were correlated with BRAF(V600E) mutation status in the univariate analysis. Meanwhile, none of the analyzed prognostic factors were correlated with K-Ras mutation status. Discussion: Although many studies suggest BRAF(V600E) and K-Ras mutations as prognostic factors in WDTC, our results are controversial. BRAF(V600E) and K-Ras mutations have no significant effects on tumor aggressiveness in Turkish patients with WDTC. Our results underline that it is too early to reach a conclusion that BRAF(V600E) and K-Ras mutations are involved with poor clinical outcomes.

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