Waldmann Elisabeth, Ferlitsch Monika, Binder Nicolas, Sellner Franz, Karner Josef, Heinisch Birgit, Klimpfinger Martin, Trauner Michael
Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
Digestion. 2015;91(4):286-93. doi: 10.1159/000381284. Epub 2015 Apr 28.
To investigate tumor and patient characteristics of individuals with mismatch repair (MMR)-deficient colorectal carcinomas.
We immunhistochemically investigated tissue samples of 307 consecutive patients with colorectal cancer for defects in DNA MMR proteins (hMLH1, hMSH2, hMSH6, hPMS2) and those with mutations further for microsatellite instability (MSI) and BRAF V600E mutations.
32/308 (10.4%) tumors showed MMR deficiency. Seventy five percent (n = 24) had loss of hMLH1 and hPMS2 expression, 3% (n = 1) of hPMS2 alone, 18.8% (n = 6) of hMSH6 and hMSH2, 3% (n = 1) of hMSH2 alone. All MMR-deficient tumors showed high MSI. These tumors occurred preferably in the right-sided colon, in women and showed specific histological features. We obtained the family history of 18/32 patients; 2 (11.1%) met Amsterdam Criteria, 5 (27.8%) Bethesda Guidelines and 6 (33.3%) revised Bethesda Guidelines. BRAF V600E mutations were found in 16 (67%) of hMLH1 and none of the hMSH2 deficient tumors.
We suggest using immunhistochemical testing of tumor tissues with subsequent MSI analysis, which may be justified as a screening method for MMR deficiency in colorectal cancer, since it identifies patients with possibly hereditary defects and unalike response to chemotherapy.
研究错配修复（MMR）缺陷型结直肠癌患者的肿瘤及患者特征。
我们采用免疫组织化学方法对307例连续的结直肠癌患者的组织样本进行DNA错配修复蛋白（hMLH1、hMSH2、hMSH6、hPMS2）缺陷检测，对存在突变的样本进一步检测微卫星不稳定性（MSI）和BRAF V600E突变。
308例肿瘤中有32例（10.4%）显示MMR缺陷。75%（n = 24）的肿瘤hMLH1和hPMS2表达缺失，3%（n = 1）仅hPMS2表达缺失，18.8%（n = 6）的肿瘤hMSH6和hMSH2表达缺失，3%（n = 1）仅hMSH2表达缺失。所有MMR缺陷型肿瘤均显示高度微卫星不稳定性。这些肿瘤更常见于右半结肠，女性患者居多，并具有特定的组织学特征。我们获取了32例患者中18例的家族史；2例（11.1%）符合阿姆斯特丹标准，5例（27.8%）符合贝塞斯达指南，6例（33.3%）符合修订的贝塞斯达指南。在16例（67%）hMLH1缺陷型肿瘤中发现BRAF V600E突变，而在hMSH2缺陷型肿瘤中未发现。
我们建议对肿瘤组织进行免疫组织化学检测并随后进行MSI分析，这作为结直肠癌MMR缺陷的筛查方法可能是合理的，因为它能够识别可能存在遗传性缺陷以及对化疗反应不同的患者。
