腸胃道癌症的微衛星不穩定性表現及其免疫治療相關的探討

The study of the correlation between microsatellite instability expression of gastrointestinal cancer and immunotherapy

何賜元(Tzn-Yuan Ho)

指導教授 ： 曾麗慧

國立臺灣大學/醫學院/分子醫學研究所/碩士(2016年)

https://doi.org/10.6342/NTU201602943

摘要

根據衛福部2013年國人十大死因統計，惡性腫瘤居十大死因之首，而肺癌、肝癌、結腸直腸癌佔首三位。本篇論文將探討腸胃道癌症有微衛星不穩定性(Microsatellite Instability，MSI)表現及其免疫治療的相關性，並使用文獻回顧抗程序性細胞死亡-1(anti-programmed cell death-1,anti-PD-1)免疫治療有高度微衛星不穩定性(MSI-H,MSI-high,high frequency of MSI)腸胃道癌症其可能機轉，以及目前在臺大醫院偵測了86位腸胃道癌個案及1位乳癌個案，利用聚合酶連鎖反應(PCR,polymerase chain reaction)技術作MSI test，觀察分析每個個案表現MSI-H 的頻率情形。結果顯示，在87位個案當中，其中76位患有colon cancer，包括男性38位，女性38位；男性具MSI-H 2位，MSI-H頻率為5%(2/38)；女性具MSI-H 2位，MSI-H頻率為5%(2/38)，總共colon cancer MSI-H有4位，頻率佔5%(4/76)。而另外9位gastric cancer個案，男性7位，女性2位；男性具MSI-H 1位，MSI-H頻率為14.3%(1/7) ，女性皆無MSI-H表現。其餘在台大個案gallbladder cancer及breast cancer 各佔1位，並未發現有MSI-H的表現。而colon cancer MSI-H頻率5% in NTUH，與西方國家15-20% MSI-H在colon cancer的比率相比較低的原因是否與種族不同有關，還有待進一步再查証。

關鍵字

微衛星不穩定性 ； 高度微衛星不穩定性 ； 大腸癌 ； 胃癌 ； 聚合?連鎖反應 ； 免疫治療 ； 抗程序性細胞死亡-1

並列摘要

According to Ministry of Health and Welfare statistics, of the top ten leading causes of death in Taiwan in 2013, malignant tumor was the first among them. Lung cancer, hepatocellular carcinoma and colorectal cancer accounted for the top three.This thesis investigates the correlation of gastrointestinal cancer with the expression of microsatellite instability with immunotherapy and analyzes the documentation in literature of the possible mechanism by anti PD-1 immunotherapy managing gastrointestinal cancer with MSI-H. In NTUH, we detected 86 cases of gastrointestinal cancer and one case of breast cancer by using PCR-based method to use MSI testing to detect the MSI-H frequency. Among the 86 cases, 76 were colon cancer cases (38 male, 38 female).Two cases with MSI-H were detected in males frequency 5%(2/38), and two cases with MSI-H also were detected in females frequency 5%(2/38). MSI-H frequency of total colon cancer was 5% (4/76).Of the other 9 cases of gastric cancer, seven males and two females, one of seven males was detected with MSI-H frequency 14.7%(1/7). No MSI-H result was detected in a female. Of the two other cancers, one gallbladder cancer and one breast cancer were detected without expression of MSI-H. A racial difference may account for the result of 5% MSI-H frequency in colon cancer compared with the 15-20% of MSI-H frequency in western.This needs further investigation.

並列關鍵字

MSI (Microsatellite Instability) ； MSI-H (high frequency of MSI) ； colon cancer ； gastric cancer ； PCR ； immunotherapy ； anti-PD-1(anti-programmed cell death-1)

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