Analysis of screening methods for DNA mismatch repair gene deletion in colorectal cancer / 中国肿瘤临床

ABSTRACT

Objective: Here, we aimed to analyze the two most commonly used methods for screening DNA mismatch repair (MMR) gene deletions in colorectal cancer to establish a more cost-effective strategy. Methods: A total of 223 patients with colorectal cancer were recruited from the First Affiliated Hospital of Xinjiang Medical University for this study from September 2018 to September 2019. Using the Ventana BenchMark ULTRA automatic immunohistochemistry platform, the expression levels of MLH1, MSH2, PMS2, and MSH6 proteins were assessed, and the microsatellite instability (MSI) status of the tumors was then determined through PCR capillary electrophoresis. Results: Among the 223 patients with colorectal cancer, 27 (12.1%) had MMR deficiency (dMMR) and 196 (87.9%) had MMR proficiency (pMMR). The missing rates of MLH1, MSH2, MSH6, and PMS2 were estimated as 9.0% (20/223), 1.8% (4/223), 2.7% (6/223), and 9.4% (21/223), respectively. The sensitivity and specificity of the two-antibody test employing antibodies against only PMS2 and MSH6 for screening dMMR colorectal cancer were the same as those of the four-antibody test. Twenty-seven cases exhibited high microsatellite instability (MSI-H) (12.1%) and 196 cases exhibited microsatellite stability (MSS) (87.9%). However, no case exhibited low microsatellite stability (MSI-L). The sensitivities of BAT-25, BAT-26, NR-21, NR-24, NR-27, and MONO-27 were 88.9%, 92.6%, 96.3%, 70.4%, 92.6%, and 77.8%, respectively. When MSI was defined using three markers, NR-21, NR-27, and BAT-26, with at least one of the three exhibiting instability, the results were the same as those obtained using the six-marker group. Conclusions: The proposed two-marker detection strategy provides a simple, reliable, and low-cost method for the identification of dMMR/MSI in colorectal cancer.