Colorectal carcinoma from Saudi Arabia Analysis of MLH-1, MSH-2 and p53 genes by immunohistochemistry and tissue microarray analysis Khawla S. Al-Kuraya, MD, FCAP, Prashant P. Bavi, MD, Adnan A. Ezzat, MD, Fouad A. Al-Dayel, MD, FRCPA, Shahab Uddin, PhD, Valerie L. Atizado, BS, Naif A. Al-Jomah, BSc, Samir S. Amr, MD, FCAP, Salwa S. Sheikh, MD, FCAP, Guido Sauter, MD, Ronald Simon, PhD. C olorectal cancer is the fourth most common cancer across all age groups in Saudi Arabia. 1 According to established models, colorectal cancers can be subdivided into 2 distinct forms: those From the Research Centre (Al-Kuraya, Bavi, Uddin, Atizado, Al-Jomah), Medical and Clinical Operations (Ezzat), Pathology and Laboratory Medicine (Al-Dayel), King Faisal Specialist Hospital and Research Centre, Riyadh, Pathology Services Division (Amr, Sheikh), Saudi Aramco, Dhahran Health Centre, Dhahran, Kingdom of Saudi Arabia, and the Department of Pathology (Sauter, Simon), University Medical Center Hamburg Eppendorf, Ham- burg, Germany. Received 26th September 2005. Accepted for publication in final form 29th January 2006. Address correspondence and reprint request to: Dr. Khawla S. Al-Kuraya, Director, Biological Repository Centre and Director, Research Centre at King Fahad National Centre for Childrenʼs Cancer and Research, King Faisal Specialist Hospital and Research Centre, MBC 98-16, PO Box 3354, Riyadh 11211, Kingdom of Saudi Arabia. Tel. +966 (1) 2294444 Ext. 51813, +966 (1) 2055166. Fax. +966 (1) 2055170. E-mail: kkuraya@kfshrc.edu.sa 323 belonging to the chromosomal instability pathway/ microsatellite stable (MSS), and those belonging to the microsatellite instability (MSI) pathway. 2 The first and more common pathway is characterized Objective: To document the incidence and role of p53 and DNA mismatch repair proteins in colorectal carcinomas, and to evaluate the relative frequency of major molecular pathways in colorectal cancers from Saudi Arabia. Methods: We collected the formalin fixed, paraffin embedded tissues from 154 colorectal tumors (83 patients from King Faisal Specialist Hospital and Research Centre and 71 from Saudi Aramco Dhahran Health Centre) between January 1989 and December 2003. We analyzed the p53 and mismatch repair gene expression (hMSH-2, hMLH-1) by immunohistochemistry in tissue microarray format. Results: Expression loss of at least one mismatch repair gene was found in 33.8% of cases and significantly associated with the right-sided tumor location (p=0.0047). The p53 positivity was observed in 57.5% of tumors, and ABSTRACT was inversely linked to expression loss of mismatch repair genes (p=0.0102). Conclusion: The strong confirmation of the previously established associations between tumor phenotype, and mismatch repair gene alteration provided strong evidence for the validity of our experimental approach. Together with the higher incidence of right sided location in Saudi (46.6%) than in Western colon cancers (34.9%), the observed high prevalence of mismatch gene expression loss in Saudi tumors argues for a higher importance of microsatellite instability in this population. If confirmed, it will be interesting to see whether an increased level of familial or sporadic microsatellite instability cases is causing this variation. Saudi Med J 2006; Vol. 27 (3): 323-328