Microsatellite instability in primary and metastatic colorectal cancers.

Microsatellite instability characterizes a sub-set of sporadic colorectal cancers (CRCs) as well as CRCs from patients with hereditary non-polyposis colorectal cancer (HNPCC). In order to clarify when the cells acquire a replication-error phenotype (RER) during colorectal-tumor progression, we examined the incidence of RER in 80 primary tumors and 36 liver metastases at 8 microsatellite loci; 1 mono-, 5 di-, 1 tetra- and 1 pentanucleotide. RER were detected in 20.1% (17/80) of primary tumors, including 5 tumors showing RER at 2 or more loci (RER2), while the incidence of RER in liver metastases (22.2%, 8/36) was almost the same as that in primary tumors, and there was only one RER2 case in metastases. There were 3 cases in which both primary tumors and liver metastases had the same type of RER at the same locus, and there were 2 cases that showed RER in primary tumors but not in liver metastases. In contrast, there was no case in which RER was detected in a metastasis but not in the corresponding primary tumor. The RER phenotype did not show correlation with any clinicopathological parameters of cancer-cell aggressiveness, such as clinical staging, histological grade and survival. These results indicate that a sub-set of CRCs acquire the RER phenotype in the relatively early stages of colorectal carcinogenesis, and that the RER phenotype is not associated with aggressiveness of CRCs.