갑상선 유두암의 예후 예측 인자로서 BRAFV600E 돌연변이의 역할
Role of BRAFV600E Mutation as a Marker for Prognostic Stratification of Papillary Thyroid Carcinoma
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Purpose: Papillary thyroid carcinoma (PTC) is the most common malignant tumor of the thyroid and BRAFV600E mutation is the most frequent genetic alteration in PTC. BRAFV600Emutation has been demonstrated as a prognostic biomarker for prediction of poor clinicopathological outcomes, such as increased incidence of extrathyroidal extension, lymph node metastasis, and advanced stage. However, there is conflicting literature regarding the association of BRAFV600E mutation and aggressive clinicopathological features. In this study, we investigated the prevalence of BRAFV600E mutation in PTC and determined the association of BRAF mutation with indicators of poor prognosis for PTC.Methods: We reviewed 1009 patients with PTC, who underwent thyroid surgery at Kyungpook National University Hospital between January 2013 and March 2014. BRAFV600E mutation analysis was performed using real-time polymerase chain reaction based amplification of DNA extracted from paraffin-embedded tumor specimens. Results: BRAFV600E mutation was detected in 863 (85.5%) patients. In univariate analysis, histologic subtype, extrathyroidal extension, and advanced stage showed significant association with BRAFV600E mutation. In addition, concurrent Hashimoto’s thyroiditis showed an association with low prevalence of BRAFV600E mutation. However, no stati-stically significant association was observed for age, gender, multifocal or bilateral tumor, and lymph node metastasis. Multivariate analysis showed an independent association of extrathyroidal extension with BRAFV600E mutation.Conclusion: In this study, extrathyroidal extension of PTC is an independent prognostic factor associated with BRAFV600E mutation status. However, conduct of further large scale studies with long term follow up is required before the BRAF mutation can be conclusively recommended as a prognostic biomarker.
Abstract
Purpose: Papillary thyroid carcinoma (PTC) is the most common malignant tumor of the thyroid and BRAFV600E mutation is the most frequent genetic alteration in PTC. BRAFV600Emutation has been demonstrated as a prognostic biomarker for prediction of poor clinicopathological outcomes, such as increased incidence of extrathyroidal extension, lymph node metastasis, and advanced stage. However, there is conflicting literature regarding the association of BRAFV600E mutation and aggressive clinicopathological features. In this study, we investigated the prevalence of BRAFV600E mutation in PTC and determined the association of BRAF mutation with indicators of poor prognosis for PTC.Methods: We reviewed 1009 patients with PTC, who underwent thyroid surgery at Kyungpook National University Hospital between January 2013 and March 2014. BRAFV600E mutation analysis was performed using real-time polymerase chain reaction based amplification of DNA extracted from paraffin-embedded tumor specimens. Results: BRAFV600E mutation was detected in 863 (85.5%) patients. In univariate analysis, histologic subtype, extrathyroidal extension, and advanced stage showed significant association with BRAFV600E mutation. In addition, concurrent Hashimoto’s thyroiditis showed an association with low prevalence of BRAFV600E mutation. However, no stati-stically significant association was observed for age, gender, multifocal or bilateral tumor, and lymph node metastasis. Multivariate analysis showed an independent association of extrathyroidal extension with BRAFV600E mutation.Conclusion: In this study, extrathyroidal extension of PTC is an independent prognostic factor associated with BRAFV600E mutation status. However, conduct of further large scale studies with long term follow up is required before the BRAF mutation can be conclusively recommended as a prognostic biomarker.
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