Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan.
Curr Genomics. 2009 Apr;10(2):127-32. doi: 10.2174/138920209787847069.
Some cases of endometrial cancer are associated with a familial tumor and are referred to as hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome). Such tumors are thought to be induced by germline mutation of the DNA mismatch repair (MMR) gene, but many aspects of the pathology of familial endometrial cancer are unclear and no effective screening method has been established. However, the pathology of endometrial cancer with familial tumor has been progressively clarified in recent studies. At present, about 0.5% of all cases of endometrial cancers meet the clinical diagnostic criteria for HNPCC. A recent analysis of the three MMR genes (hMLH1, hMSH2 and hMSH6) revealed germline mutations in 18 of 120 cases (15.0%) of endometrial cancer with familial accumulation of cancer or double cancer, with a frameshift mutation of the hMSH6 gene being the most common. Many cases with mutation did not meet the current clinical diagnostic criteria for HNPCC, indicating that familial endometrial cancer is often not diagnosed as HNPCC. The results suggest that the hMSH6 gene mutation may be important in carcinogenesis in endometrial cancer and germline mutations of the MMR gene may be more prevalent in cases associated with familial accumulation of cancer. An international large-scale muticenter study is required to obtain further information about the pathology of endometrial cancer as a familial tumor.
有些子宫内膜癌与家族性肿瘤有关，被称为遗传性非息肉病性结直肠癌（HNPCC 或 Lynch 综合征）。这些肿瘤被认为是由 DNA 错配修复（MMR）基因突变引起的，但家族性子宫内膜癌的许多病理方面尚不清楚，也没有建立有效的筛查方法。然而，近年来对家族性肿瘤相关子宫内膜癌的病理学研究已经逐渐阐明。目前，约有 0.5%的子宫内膜癌病例符合 HNPCC 的临床诊断标准。最近对三个 MMR 基因（hMLH1、hMSH2 和 hMSH6）的分析显示，在 120 例具有癌症或双癌家族聚集的子宫内膜癌中，有 18 例（15.0%）存在胚系突变，其中 hMSH6 基因突变以移码突变最为常见。许多有突变的病例不符合当前 HNPCC 的临床诊断标准，表明家族性子宫内膜癌通常不被诊断为 HNPCC。这些结果表明，hMSH6 基因突变可能在子宫内膜癌的癌变过程中起重要作用，并且与家族性肿瘤相关的病例中 MMR 基因突变可能更为普遍。需要进行国际大规模多中心研究，以获得更多关于家族性肿瘤的子宫内膜癌病理学信息。
