Expression and correlation of phosphorylation extracellular signal-regulated kinase and monopolar spindle 1 in colorectal cancer with wild type or BRAF V600E mutation / 肿瘤研究与临床

ABSTRACT

Objective To determine the correlation between phosphorylation extracellular signal-regulated kinase (p-Erk) and monopolar spindle 1 (Mps1) in colorectal cancer patients with the BRAF V600E mutation or not, and to explore the relationship between the expression of p-Erk and Mps1 with the clinicopathological features and prognosis of colorectal cancer patients. Methods Two hundred and eighty-eight paraffin-embedded tissue sections containing both the carcinoma and its adjacent non-neoplastic colorectal tissue were collected from January 2009 to June 2015 in the First Hospital of Shanxi Medical University. BRAF mutation was detected by Sanger sequencing. Kaplan-Meier survival analysis was used to analyze the correlation between BRAF V600E and prognosis. Immunohistochemistry was used to detect the expression level of p-Erk and Mps1 in colorectal cancer with wild type or BRAF V600E mutation. The correlation between p-ERK and Mps1 expression was analyzed by using linear regression analysis. Results The BRAF V600E mutation rate was 5.2 % in colorectal carcinomas. In addition, the poorly differentiated tumours and mucinous tumours had higher incidence of BRAF mutations than well differentiated tumours and non-mucinous tumours respectively [14.3 % (9/63) vs. 2.7 % (6/225),χ 2= 11.208,P = 0.001; 25.0 % (6/24) vs. 3.4 %(9/264),χ 2=16.630,P <0.001). The positive rate of p-Erk and Mps1 in colorectal carcinomas with BRAF V600E was significantly higher than that in colorectal carcinomas with BRAF WT (14/15 vs. 3/15, P <0.05; 15/15 vs. 3/15, P < 0.05]. It was found that the p-Erk expression correlated positively to the Mps1 expression (R2= 0.419,P < 0.001). The expressions of p-Erk protein in poorly differentiated adenocarcinoma was significantly higher and mucinous adenocarcinoma than those in high differentiated adenocarcinoma and non-mucinous adenocarcinoma (χ 2= 6.679, P = 0.01; χ 2= 5.735, P = 0.017), as well as in the group with lymph node metastasis than without lymph node metastasis (χ 2=5.436, P =0.02). Positive rate of Mps1 in poorly differentiated carcinoma was higher than that in well differentiated adenocarcinoma of colorectal carcinomas (χ 2=7.950, P =0.009). The Kaplan-Meier survival analysis indicated that patients with BRAF V600E had a worse survival rate than BRAF WT patients. Conclusions BRAF V600E may play an important role in specific pathological kinds of colorectal carcinomas, which is expected to be an independent prognostic factor. The expression of p-Erk is significantly correlated with Mps1 in colorectal carcinomas, suggesting that Mps1 may become a new potential target for targeted therapy.