Contrasting molecular pathology of colorectal carcinoma in Egyptian and Western patients

Colorectal carcinoma is uncommon in Egypt, but a high proportion of cases o ccurs before age 40 years and in the rectum. We compared the molecular path ology of 59 representative Egyptian patients aged 10-72 to Western patients with sporadic, young-onset, or hereditary non-polyposis colorectal cancer syndrome (HNPCC) -associated carcinoma and found significant differences. M ost Egyptian cancers were rectal (51%) and poorly differentiated (58%). Hig h levels of microsatellite instability (MSI-H) were frequent (37%) and attr ibutable in some cases (36%) to methylation of the promoter of the hMLH1 mi smatch repair gene, but no MSI-H cancer had loss of hMSH2 mismatch repair g ene product of the type seen with germline hMSH2 mutation in HNPCC. K-ras m utation was uncommon (11%). In subset analyses, high frequencies of MSI-H i n rectal carcinomas (36%) and p53 gene product overexpression in MSI-H canc ers (50%) were found. MSI-H and K-ras mutation in Egyptians under age 40 we re unusual (17% and 0%, respectively), and schistosomiasis was associated w ith MSI and K-ras mutation. Cluster analysis identified 2 groups: predomina ntly young men with poorly differentiated mucinous and signet-ring cell col orectal carcinoma lacking K-ras mutation; older patients who had well- or m oderately differentiated adenocarcinoma often with MSI-H, K-ras mutation an d schistosomiasis. Our findings show that the molecular pathology of colore ctal cancer in older as well as younger Egyptians has unique differences fr om Western patients, and schistosomiasis influences the molecular pathogene sis of some tumours. (C) 2001 Cancer Research Campaign http://www.bjcancer. com.