散发性结直肠癌组织病理学特征及微卫星不稳定状态分析400例

Histopathologic features and microsatellite instability of sporadic colorectal carcinoma: An analysis of 400 cases

目的:探讨高度微卫星不稳定性(high level of micro satellite instability,MSI-H)结直肠癌临床病理学特征.应用免疫组织化学方法检测肿瘤组织中DNA错配修复蛋白缺失表达,判断肿瘤MSI状态,建立筛选与遗传相关结直肠癌常规诊断流程.方法:分析临床特点,光镜下观察肿瘤组织形态学特征,免疫组织化学SP法分析肿瘤DNA错配修复蛋白表达缺失情况,判断肿瘤MSI状态,荧光定量PCR法进一步证实肿瘤MSI状态.结果:400例散发性结直肠癌,以男性左半结肠多见,免疫组织化学方法检测到MSI-H18例,MSI-L98例,MSS284例,MSI-H肿瘤以老年女性左半结肠多见.MSI-H结直肠癌形态学多见绒毛乳头状结构,高、低分化,黏液腺癌、印戒细胞癌或伴有黏液分化,肿瘤上皮内淋巴细胞浸润、肿瘤间质内见Crohn样淋巴细胞反应及瘤周淋巴浆细胞浸润明显,多数缺乏坏死.荧光定量PCR法进一步对18例MSI-H肿瘤进行分析,证实MSI-H7例,MSI-L1例,MSS6例,同时发现4例肿瘤存在等位基因杂合性缺失.结论:散发性MSI-H结直肠癌与病理形态学具有明显相关性,与患者年龄、性别、部位无显著相关.结合形态学及免疫组织化学检测错配修复蛋白可作为判断MSI-H肿瘤的常规筛查方法,对患者进行临床监控、个体化治疗及筛选与遗传相关结直肠癌具有重要临床意义,但对MSI-H肿瘤最终确诊及是否与遗传相关仍需进行分子生物学方法检测进一步证实.

AIM： To investigate the clinicopathologic features of sporadic colorectal carcinoma with high level of microsatellite instability （MSI-H）, detect deficient expression of DNA mismatch repair protein, predict tumor microsatellite instability （MSI） status, and create a platform for diagnosis and screening of genetic colorectal carcinoma. METHODS： Clinical data for 400 cases of sporadic colorectal carcinoma were analyzed. All cases underwent histological assessment. The deficiency expression of mismatch repair protein was detected by immunohistochemistry. The MSI status of carcinoma was predicted and then confirmed by PCR. RESULTS： Male patients and left-side location predominated in the present series. Of 400 cases of sporadic colorectal carcinoma, 18 cases of MSI-H, 98 cases of MSI-L and 284 cases of MSS were detected by immunohistochemistry. Pathological features of MSI-H colorectal carcinoma included villous and papilloma structures, poor or good differentiation, mucinous type, signet-cell carcinoma or any mucinous differentiation, increased tumor-infiltrating lymphocytes （TIL cells）, the presence of Crohn-like reaction, and the lack of necrosis. PCR analysis confirmed that there were 7 cases of MSI-H tumors, 1 case of MSI-L, 6 cases of MSS and 4 cases of allele of heterozygosity. CONCLUSION： Sporadic MSI-H colorectal carcinoma has unique morphology, but shows no correlation with patient age, sex, and tumor size. Morphological assessment with immunohisto-chemistry can be used as a routine method for screening MSI-H and genetic colorectal carcinoma and guiding individualized treatment.