Abstract
We report a case which fulfilled with Amsterdam criteria for HNPCC and in which five metachronous primary cancers in colon, lung and duodenum had been resected so far. The patient had undergone operations for ascending colon cancer at age of 32, right lung cancer (adenocarcinoma) at age of 53, early cancer of descending colon at age of 57, advanced cancer of descending colon at age of 58, duodenal cancer at age of 59. His mother, elder brother and younger brother also had histories of colon cancers, therefore, his family history shows that 4 colon cancer cases had accumulated in successive generations. We extracted DNA from formalin-fixed, paraffin embedded tissues which were resected in operations and analyzed microsatellite instability (MSI) using 5 fluorescencelabeled microsatellite markers. Some of the specimens were judged as MSI High and immunohistochemical study showed the lack of protein product of hMLH1,
suggesting the defect of hMLH1 gene. Then, we assumed that there might be a mutation in hMLH1 gene, however, germline mutation was detected neither in hMLH1 nor hMSH2 by direct sequencing. It is necessary for us to recognize the existence of such case which is compatible with HNPCC criteria but could not be shown to harbour any germline mutation of hMLH1 and/or hMSH2 gene. A new, highly-efficient method for detection of disorder of mismatch repair gene(s) is needed and also useful surveillance protocol could be established in near future.
