Proliferation, apoptosis, and survival in high-level microsatellite instability sporadic colorectal cancer

Sporadic colorectal cancer (CRC) characterized by high-level DNA microsatel lite instability (MSI-H) has a favorable prognosis. The reason for this MSI -H survival advantage is not known. The aim of this study was to correlate proliferation, apoptosis, and prognosis in CRC stratified by MSI status. Th e proliferative index (PI) was measured by immunohistochemical staining wit h the Ki-67 antibody in a selected series of 100 sporadic colorectal cancer s classified according to the level of MSI as 31 MSI-H, 29 MSI-Low (MSI-L), and 40 microsatellite stable (MISS). The Ki-67 index was significantly hig her in MSI-H cancers (P < 0.0001) in which the PI was 90.1 <plus/minus> 1.2 % (mean +/- SE) compared with 69.5 +/- 3.1 % and 69.5 +/- 2.3 % in MSI-L an d MSS subgroups, respectively. There was a positive linear correlation betw een the apoptotic index (AI) and PI (r = 0.51; P < 0.001), with MSI-H cance rs demonstrating an increased AI:PI ratio indicative of a lower index of ce ll production. A high PI showed a trend toward predicting improved survival within MSI-H cancers (P = 0.09) but did not predict survival in MSI-L or M SS cancers. The Al was not associated with survival in any MSI subgroup. In conclusion, this is the first study to show that sporadic MSI-H cancers ar e characterized by a higher AL:PI ratio and increased proliferative activit y compared with MSI-L and MSS cancers, and that an elevated PI may confer a survival advantage within the MSI-H subset.