Genetic alterations and MSI status in primary, synchronous, and metachronous tumors in a family with hereditary nonpolyposis colorectal cancer (HNPCC)

In colorectal cancer, different levels of microsatellite instability (MSI) have been described: high-frequency MSI, low-frequency MSI, and stable microsatellites. MSI-H characterizes a unique clinical and pathologic phenotype known as hereditary nonpolyposis colorectal cancer syndrome (HNPCC). In this case, an increased incidence of synchronous and metachronous tumors has been reported, but there are few reports with standardized criteria of MSI in HNPCC-associated tumors. The authors attempted to establish whether tumors of the HNPCC spectrum with different levels of MSI could predict the development of metachronous carcinomas. We have examined the levels of MSI at loci frequently affected in colorectal cancers in primary, synchronous, and metachronous tumors in a family that fulfils the Amsterdam criteria for HNPCC. This family presents colorectal cancers, HNPCC-extracolonic tumors (endometrial and ureter), and tumors (breast and bladder) not described in the HNPCC spectrum. The tumors exhibited MSI-H, irrespective of their location and regardless whether they were primary, synchronous, or metachronous, with the only exception of both endometrial tumors that showed low-frequency MSI tumors (MSI-L). Our results suggest that not only colorectal tumors with MSI-H result in a potential marker for the determination of high-risk individuals for metachronous and synchronous tumors, but also MSI-L endometrial tumors might be considered as indicative of high-risk individuals.