Analysis of clinicopathological features and prognostic factors for metastatic colorectal cancer by using biomarkers as IHC of MMR, PD-L1 and TIL.

• Main Authors: Ching-Ming Chang, 張景明
• Other Authors: 林赫
• Format: Others
• Language: zh-TW
• Published: 2019
• Online Access: http://ndltd.ncl.edu.tw/cgi-bin/gs32/gsweb.cgi/login?o=dnclcdr&s=id=%22107NCHU5105043%22.&searchmode=basic

碩士 === 國立中興大學 === 生命科學院碩士在職專班 === 107 === The incidence rate of colorectal cancer is raising in Taiwan, and it ranks second of the top 10 cancers. The average survival time of metastatic colorectal cancer is beyond 2 years in current treatment modalities including surgery, chemotherapy and targeted therapy. In recent years, immune checkpoint inhibitors bring great progress in improving response rate and prolonging survival time in many cancers, such as melanoma, lung cancer, head & neck cancer and urothelial carcinoma. Until the application of mismatch repair (MMR), immune checkpoint inhibitors are found to significantly improve the treatment outcome in colorectal cancer with deficiency MMR (dMMR). Furthermore, tumor-infiltrating lymphocytes (TIL) has been proven to play a major role in many cancers. Meanwhile, the expression level of progreammed death-ligand 1 (PD-L1) in tumor cells may predict the treatment response of immune checkpoint inhibitors, and this applied to many cancers, esp. for lung cancer. Thus the purpose of our study is to explore the prognostic factors of metastatic colorectal cancer by collecting the basic clinical and pathologic features (include TIL) and performing immunohistochemistry analysis for MMR panel and PD-L1 of tumor specimens. Totally, 93 patients were included in our study, and clinical data were collected. We performed immunohistochemistry stain from tumor specimens for MMR panel (MLH-1、MSH-2、MSH-6、PMS2), PD-L1 expression (both in tumor cell (TC-PDL1) and TIL (TIL-PDL1)) and TIL, and then interpreted. Then variables were analyzed for survival analysis by Cox proportional hazards model. Age older than 60 years-old, lymph node invasion more than 4, grade 3 tumor and TIL－ were 4 poor prognostic factors by univariate analysis. However TIL－ is the only poor prognostic factor reaching statistically significance in multivariate analysis. Gender, primary tumor site, primary tumor size, status of distant metastasis, K-RAS mutation, MMR, TC-PDL1, TIC-PDL1 and initial chemotherapy were not prognostic factors for overall survival. Although MMR, TC-PDL1 are good at predicting treatment response for immune checkpoint inhibitors in many clinical trials, but they are not prognostic in our metastatic colorectal cancer study. In our study, TIL+ cancer has good prognosis in metastatic colorectal cancer which is less reported in available literatures. The good prognostic role of TIL+ is also found in other cancer types by many studies. We found that most of the dMMR patients are TIL+. However, the dMMR patient number is small, it is either difficult to do correlation analysis between dMMR and TIL or to perform survival analysis using MMR and TIL. We suggest large-scale prospective randomized-controlled trials with more patient numbers and immune checkpoint inhibitors intervention in the future.