Feng Lu, Li Mei, Zhang Qiu-Ping, Piao Zheng-Ai, Wang Zhao-Hui, Lv Shen
Laboratory Center, The Second Affiliated Hospital of Dalian Medical University, Liaoning 116027.
Oncol Lett. 2011 Jan;2(1):59-63. doi: 10.3892/ol.2010.219. Epub 2010 Nov 23.
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.
V-raf鼠肉瘤病毒癌基因同源物B1(BRAF)是丝裂原活化蛋白激酶(MAPK)途径的重要成员,其点突变(V600E)是甲状腺乳头状癌(PTC)中常见的基因事件。研究人员表明,BRAF表达水平的变化独立于V600E突变。这些变化参与了甲状腺癌的发病机制。本研究评估了BRAF、增殖细胞核抗原(PCNA)和hMSH2作为预测PTC转移潜能标志物的可行性。采用免疫组织化学方法,研究了70例PTC组织和29例结节性甲状腺肿(NG)组织中BRAF、PCNA和hMSH2蛋白的表达。结果表明:i)PTC中BRAF、PCNA和hMSH2表达的阳性率显著高于NG(分别为P=0.000、P=0.000和P=0.003);ii)淋巴结转移(LNM)组中BRAF表达的阳性率显著高于非LNM组(P=0.019);iii)LNM的PTC患者诊断时的年龄显著大于无LNM的患者(P=0.021);iv)BRAF表达的阳性率与PCNA和hMSH2表达的阳性率显著相关(分别为P=0.000和P=0.019)。总之,BRAF、PCNA和hMSH2的过表达似乎是PTC致癌的分子事件。BRAF过表达的老年患者似乎是PTC转移的高危人群。检测BRAF表达可能有助于预测癌的转移潜能。