Utility of BRAF protein overexpression in predicting the metastasis potential of papillary thyroid carcinoma

Abstract

V-raf murine sarcoma viral oncogene homolog B1 (BRAF) is a significant member of the MAPK pathway, the point mutation (V600E) of which is a common genetic event in papillary thyroid carcinoma (PTC). Investigators showed that the variations in BRAF expression levels were independent of the V600E mutation. These variations were involved in the pathogenesis of thyroid carcinomas. This study evaluated the feasibility of BRAF, proliferating cell nuclear antigen (PCNA) and hMSH2 as markers for the prediction of the metastatic potential of PTC. Using immunohistochemistry, the expression of BRAF, PCNA and hMSH2 proteins was studied in 70 PTC and 29 nodular goiter (NG) tissues. The results indicated that i) the positive rate of BRAF, PCNA and hMSH2 expression in PTCs was significantly higher than that in NGs (P=0.000, P=0.000 and P=0.003, respectively), ii) the positive rate of BRAF expression in the lymph node metastasis (LNM) group was significantly higher than that in the non-LNM group (P=0.019), iii) the age at diagnosis of PTC patients with LNM was significantly older compared to that without LNM (P=0.021) and iv) the positive rate of BRAF expression significantly correlated with that of PCNA and hMSH2 expression (P=0.000 and P=0.019, respectively). In conclusion, BRAF, PCNA and hMSH2 overexpression appeared to be molecular events of PTC carcinogenesis. Older patients with BRAF overexpression appear to be a high-risk group for PTC metastasis. Detection of BRAF expression is likely to aid in the prediction of the metastatic potential of the carcinoma.

Figure 1

Immunohistochemical profiling of the positive expression of (A, B and C) BRAF, PCNA and hMSH2 protein in papillary thyroid carcinomas and (D, E and F) the negative expression in NGs. Magnification, ×200.