Huang Wen-ting, Qiu Tian, Ling Yun, Shi Su-sheng, Guo Lei, Zheng Bo, Lü Ning, Ying Jian-ming
Department of Pathology, Cancer Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China.
Department of Pathology, Cancer Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China. E-mail:
Zhonghua Bing Li Xue Za Zhi. 2013 Oct;42(10):655-9.
To analyze immunophenotypes and gene mutations of colorectal precancerous lesions and adenocarcinoma, and to compare the difference of carcinogenetic mechanisms between the two precancerous lesions.
Fifty-three cases of colorectal serrated lesions including 30 hyperplastic polyps, 20 sessile serrated adenomas (SSA) and 3 mixed polyps were collected from January 2006 to June 2012.Forty-five cases of traditional adenomas and 50 cases of colorectal adenocarcinomas were also recruited. Thirty hyperplastic polyps, 20 cases of SSA, 3 mixed polyps and 45 traditional adenomas were investigated by immunohistochemistry for the expression of DNA mismatch repair (MMR) proteins (MLH1, MSH2 and MSH6) and DNA methyltransferase MGMT. Mutations of KRAS, BRAF and PIK3CA genes in 10 cases of SSAs, 10 traditional adenomas, 1 mixed polyps and 50 colorectal adenocarcinomas were analyzed by PCR followed by direct Sanger sequencing.
(1) Only 3 cases of hyperplastic polyps lost MLH1 expression, and none of SSAs or traditional adenomas showed loss of MLH1. The negative expression rates of MSH2, MSH6 and MGMT in hyperplastic polyps and SSA were significantly higher than those of traditional adenomas. (2) KRAS mutation was found in 5/10 cases of SSAs, 5/10 traditional adenomas and 1/1 mixed polyps. (3) Colorectal adenocarcinomas harbored the mutations of KRAS (48%, 24/50), BRAF (6%, 3/50) and PIK3CA (4%, 2/50).
Immunophenotypic and gene mutation profiles are different between colorectal serrated lesion and traditional adenoma. Alterations of MMR and MGMT expression play important roles in the pathogenesis of "serrated neoplasm". KRAS mutation is a significant genetic change in the early phase of colorectal carcinogenesis.
分析结直肠癌前病变及腺癌的免疫表型和基因突变情况，比较两种癌前病变致癌机制的差异。
收集2006年1月至2012年6月间53例结直肠锯齿状病变，其中包括30例增生性息肉、20例无蒂锯齿状腺瘤（SSA）和3例混合性息肉。同时纳入45例传统腺瘤和50例结直肠癌。采用免疫组化方法检测30例增生性息肉、20例SSA、3例混合性息肉和45例传统腺瘤中DNA错配修复（MMR）蛋白（MLH1、MSH2和MSH6）及DNA甲基转移酶MGMT的表达。采用聚合酶链反应（PCR）及直接桑格测序法分析10例SSA、10例传统腺瘤、1例混合性息肉及50例结直肠癌中KRAS、BRAF和PIK3CA基因的突变情况。
（1）仅3例增生性息肉出现MLH1表达缺失，SSA及传统腺瘤均未出现MLH⁃1表达缺失。增生性息肉及SSA中MSH2、MSH6及MGMT的阴性表达率显著高于传统腺瘤。（2）10例SSA中有5例、10例传统腺瘤中有5例及1例混合性息肉中检测到KRAS突变。（3）结直肠癌中KRAS、BRAF及PIK3CA基因的突变率分别为48%（24/50）、6%（3/50）和4%（2/50）。
结直肠锯齿状病变与传统腺瘤的免疫表型及基因突变谱不同。MMR及MGMT表达改变在“锯齿状肿瘤”的发病机制中起重要作用。KRAS突变是结直肠癌发生早期的重要遗传学改变。
