Colorectal carcinomas from Middle East. Molecular and tissue microarray analysis of genomic instability pathways.

OBJECTIVE To evaluate the overall incidence of microsatellite instability (MSI), hereditary non polyposis colorectal cancer, and tumor supressor gene (TP53) mutations in Saudi colorectal carcinomas. METHODS We studied the MSI pathway in Saudi colorectal cancers (CRC) from 179 unselected patients using 2 methods: MSI by polymerase chain reaction, and immunohistochemistry detection of mutL homologs 1 and mutS homologs 2 proteins. The TP53 mutations were studied by sequencing exons 5, 6, 7, and 8. RESULTS Of the 150 colorectal carcinomas analyzed for MSI, 16% of the tumors showed high level instability (MSI-H), 19.3% had low-level instability (MSI-L) and the remaining 64% tumors were stable. Survival of the MSI-H group was better as compared to the MSI-L or microsatellite stable group (p=0.0217). In the MSI-H group, 48% were familial MSI tumors, which could be attributable to the high incidence of consanguinity in the Saudi population. The TP53 mutations were found in 24% of the cases studied. CONCLUSION A high proportion of familial MSI cases and a lower incidence of TP53 mutations are some of the hallmarks of the Saudi colorectal carcinomas, which need to be explored further.