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.
Keywords: HNPCC, Endometrial cancer, DNA mismatch repair gene, hMLH1,
hMSH6.
