Microsatellite instability in sporadic colon cancer is associated with an improved prognosis. Recent studies, however, have suggested that microsatellite unstable cancers with mutations in the proapoptotic gene BAX have a relatively poor prognosis, whereas those with mutations in transforming growth factor-beta receptor type II (TGFBRII) have a relatively good prognosis. Using instability in the non-coding mononucleotide repeat BAT-26 as a measure of generalized microsatellite instability, we evaluated the prognosis of unstable colon cancers with and without frameshift mutations in the coding mononucleotide repeats of BAX and TGFBRII in a population-based sample of 1,427 individuals. BAX mutations were identified in 39.0% (64/164) of unstable colon cancers, whereas TGFBRII mutations were identified in 79.3% (138/174) of unstable colon cancers. Unstable colon cancers with and without instability in BAX and TGFBRII were associated with very similar and statistically indistinguishable percentage 5-year survivals and Kaplan-Meier survival curves; stable colon cancers were associated with a significantly worse 5-year survival and Kaplan-Meier survival (P < 0.001 and P < 0.013, respectively, compared against BAT-26 unstable). The age- and stage-adjusted risk of death associated with BAX or TGFBRII mutations was not significantly different from that of unstable tumors without such mutations. We conclude that instability-induced mutations in BAX or TGFBRII do not have a significant impact on the good prognosis of colon cancers with microsatellite instability.
Copyright 2002 Wiley-Liss, Inc.