Loss of BAK expression correlates with MSI in colon cancer

Background: Genomic mutations of DNA mismatch repair enzymes are associated with genomic instability and are a common denominator of cancer resulting in familiar clustering of colon cancer also known as HNPCC. The tumors exhi bit paradoxical low incidence of somatic mutations in the p53 tumor suppres ser gene but defects of DNA repair enzymes are associated with frameshift m utations of the proapoptotic gene bar. Bar is member of the bcl-2 family wh ich can be broadly categorized as death antagonists and death agonists of p rogrammed cell death. Methods: To analyze expression of bcl-2 family members in the context of ge nomic instability samples of 61 patients with colon cancers were embedded i n formalin. Expression of bcl-2 (6-C8), bcl-xl (Santa Cruz H-62), bcl-w (Sa nta Cruz N-19) and bak (Santa Cruz G-23) were analyzed by immunohistochemis try. Further genomic instability was assessed by PCR with the reference pan el of the American Joint Commission of Cancer. Results: 22.9% of tumors showed evidence of genomic instability. No bak exp ression was seen in 56% of instable tumors and 32% of stable tumors. There was no difference in bcl-2 (14% vs. 12%) and bcl-w (0% vs. 0%) expression. Conclusion: These data suggest that genomic instability is associated with loss of bak expression in colon cancer. The lack of death agonists but not the overexpression of death antagonists might contribute to tumor progressi on in colon cancer with genomic instability.