Abstract:  Objective To investigate the expression of mutL homologous gene 1 (MLH1) in patients with gastric cancer and its predictive value for prognosis and preoperative neoadjuvant chemotherapy response. Methods A total of 323 patients who underwent radical gastrectomy in Hainan Hospital of Traditional Chinese Medicine from January 2010 to December 2016 were collected as the research objects. The expression level of MLH1 was determined by immunohistochemistry. The histological response of preoperative chemotherapy was evaluated based on the proportion of surviving cancer cells. MSI status was evaluated in tumors with negative expression of MLH1 based on the results of immunohistochemistry. The Cox regression was used to analyze the independent risk factors affecting recurrence-free survival (RFS). Results Among the 323 patients, 32 (9.9%) had negative expression of MLH1 and 291 (90.1%) had positive expression of MLH1. Among the 32 patients with MLH1 negative expression, 27 (84.3%) were MSI-H and 5 (15.7%) were MSS/MSI-L. The proportion of neoadjuvant chemotherapy responders in the MLH1 negative group was lower than that in the MLH1 positive group (21.4% vs 60.4%, P<0.001). Among patients without preoperative neoadjuvant chemotherapy (n=198), the RFS of the MLH1 negative group was longer than that of the MLH1 positive group (P<0.001). Among patients who received preoperative neoadjuvant chemotherapy (n=125), there was no statistically significant difference in RFS between the two groups (P=0.352). Multivariable Cox regression showed that patients with  MLH1 positive expression had a higher risk of recurrence than those with MLH1 negative expression (HR=2.45, 95%CI: 1.06-5.67, P=0.037). Conclusions MLH1 deletion is associated with chemotherapy resistance and the RFS after neoadjuvant chemotherapy is not prolonged. MLH1 is highly correlated with MSI status and can be a surrogate indicator of MSI. 

Key words: Gastric cancer, mutL homologous gene 1, Microsatellite instability, Prognosis, Neoadjuvant chemotherapy