Clinic-pathological characteristics of MMR protein, KRAS-NRAS-BRAF gene mutation, HER-2 and PD-L1 status in 3822 Chinese colorectal cancer patients

Abstract

ObjectivesColorectal cancer is one of the most common cancers. It is a heterogeneous tumor. The aim of this study was to investigate MMR protein expression, KRAS-NRAS-BRAF gene mutation, HER-2 and PD-L1 status in large Chinese CRC patients. MethodsWe reviewed all CRC patients who underwent surgery in Peking University Cancer Hospital between 2010 and 2018 from a prospective collected medical database. We analyzed the clinic-pathological factors associated with immunohistochemistry profiles. We analyzed KRAS-NRAS-BRAF gene changes through ARMS-PCR. ResultsIn our study, d-MMR frequency of CRC was 8%. d-MMR was more common in poorly differentiated colorectal cancer (p = 0.000), and d-MMR was more likely to occur in stage T3 + T4( p = 0.026), and p-MMR was more likely to have lymph node metastasis(p = 0.000). d-MMR was more likely to occur in the right colon, and p-MMR patients usually occur in the rectum sigmoid colon(p = 0.000). p-MMR patients were more likely to have distant metastasis (p = 0.000). We analyzed all 3822 patients with-BRAF status available by IHC, the frequency of BRAF positive expression ration was 1.4%. A total of 1068 colorectal cancer patients had gene analysis by ARMS-PCR. 484 of them had KRAS gene mutation, 28 NRAS gene mutation, 20 BRAF mutation and 536 patients had no mutation. The percentage was 45%, 2.6%, 2%, and 50%, respectively. d-MMR patients usually had BRAF gene mutation (p < 0.001). KRAS and NRAS gene mutations were not associated with MMR status (p = 0.846, p = 0.438). PD-L1 expression was higher in the female group (p = 0.034), poorly differentiated adenocarcinoma group(p = 0.026), and d-MMR group (p = 0.005). The ratio of HER-2 3 + was 1.9%, and HER-2 3 + was usually found in p-MMR group(p = 0.043). ConclusionOur data can improve deeper understanding of colorectal cancer carcinogenic factors and future therapies for colorectal cancer.