Clinical implication of the BRAF V600E mutation in papillary thyroid carcinoma
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WORLD JOURNAL OF SURGICAL ONCOLOGY
RESEARCH
Open Access
Clinical implication of the BRAFV600E mutation in papillary thyroid carcinoma Yong-Seok Kim, Jeong-Soo Kim, Ja-Seong Bae and Woo-Chan Park*
Abstract Background: The BRAFV600E mutation is the most common genetic alteration in papillary thyroid carcinoma (PTC). In recent studies, the BRAFV600E mutation has been associated with poor clinicopathological characteristics, such as lymph node metastasis, extrathyroidal extension, and advanced stage. However, other studies have failed to establish an association between the BRAFV600E mutation and clinicopathological features. Therefore, we investigated the relationship between the BRAFV600E mutation and its clinicopathological factors at a single institution. Methods: A total of 327 consecutive patients with PTC were enrolled in this study and underwent thyroid surgery at Yeouido St. Mary’s Hospital between February 2010 and December 2011. BRAFV600E mutation analysis was performed using polymerase chain reaction (PCR)-based amplification of DNA extracted from paraffin-embedded tumour specimens. Results: The BRAFV600E mutation was detected in the tumours of 241 (73.7%) patients. Lymph node metastasis, TNM stage, and multifocality were not significantly associated with the BRAFV600E mutation. However, larger tumour size, extrathyroidal extension, histologic type (classic type), and concurrent Hashimoto’s thyroiditis were associated with the BRAFV600E mutation in the univariate analysis, although no clinicopathological features were associated with the BRAFV600E mutation in the multivariate analysis. Conclusion: There was no idependent prognostic factor associated with BRAFV600E mutation status in this study. The BRAFV600E mutation is unlikely to serve as a prognostic factor for PTC. Keywords: BRAF mutation, Papillary carcinoma, Thyroid
Background Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy, accounting for 85% to 90% of all thyroid malignancies [1,2]. PTC is generally treated successfully with surgery, radioiodine ablation, and levothyroxine suppression therapy. This malignancy typically has a favourable prognosis, with an average 10-year survival rate of over 90%, although up to 35% of patients suffer from disease recurrence during long-term follow up [3]. Several genetic events have been associated with PTC, and the BRAF mutation is the most common genetic alteration detected in patients with PTC [4]. The RAF protein has three isoforms, with BRAF being the most common isoform found in thyroid follicular cells and the * Correspondence: [email protected] Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea
strongest activator of mitogen-activated protein kinase signalling [5]. The most common BRAF mutation in thyroid cancer, occurring in more than 95% of cases, is the T1799A transversion mutation in exon 15. The thymidine to adenine transversion at position 1,799 results in a valine to glutamic acid substitution at residue 600 (V600E) [4,6] and
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