Katabuchi H, van Rees B, Lambers A R, Ronnett B M, Blazes M S, Leach F S, Cho K R, Hedrick L
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Cancer Res. 1995 Dec 1;55(23):5556-60.
Endometrial carcinoma is the second most common tumor type in women with hereditary nonpolyposis colorectal carcinoma. Microsatellite instability (MI) has been observed in the inherited (hereditary nonpolyposis colorectal carcinoma-associated) form of endometrial carcinoma as well as in approximately 20% of presumably sporadic cases. Recent studies suggest that MI in many cell lines or xenografts derived from sporadic colorectal carcinomas is not attributable to mutations in four known human DNA mismatch repair (MMR) genes (hMSH2, hMLH1, hPMS1, and hPMS2). Mutational analyses of these four MMR genes in endometrial carcinomas have not been previously reported. We analyzed nine sporadic MI-positive primary endometrial carcinomas for mutations in the above four MMR genes. Mutations were detected in two tumors (in hMSH2), and both of the mutations were acquired somatically. Immunohistochemical staining revealed a lack of expression of hMSH2 protein in the two tumors containing hMSH2 mutations. Our data suggest that mutations in these four known DNA MMR genes are not responsible for MI in the majority of sporadic endometrial carcinomas displaying this phenotype.
子宫内膜癌是遗传性非息肉病性结直肠癌女性患者中第二常见的肿瘤类型。在遗传性（与遗传性非息肉病性结直肠癌相关）子宫内膜癌以及约20%的可能散发病例中均观察到微卫星不稳定性（MI）。最近的研究表明，许多源自散发性结直肠癌的细胞系或异种移植物中的MI并非归因于四种已知人类DNA错配修复（MMR）基因（hMSH2、hMLH1、hPMS1和hPMS2）的突变。此前尚未报道过对子宫内膜癌中这四种MMR基因的突变分析。我们分析了9例散发的MI阳性原发性子宫内膜癌中上述四种MMR基因的突变情况。在两个肿瘤中检测到突变（hMSH2基因），且两个突变均为体细胞获得性突变。免疫组化染色显示，在两个含有hMSH2突变的肿瘤中缺乏hMSH2蛋白表达。我们的数据表明，在大多数表现出这种表型的散发性子宫内膜癌中，这四种已知DNA错配修复基因的突变并非导致MI的原因。
