Relationship Between Expression of ras p21 Oncoprotein and Mutation Status of the K-ras Gene in Sporadic Colorectal Cancer Patients in Tunisia

Introduction: The K-ras proto-oncogene encodes a protein (p21-ras) belonging to the family of GTP/GDP-binding proteins with GTPase activity. The activation of ras family genes plays an important role in colorectal tumorigenesis. Frequency of K-ras mutations and overexpression of the protein in colorectal cancer (CRC) vary between 14% and 50% and between 29% and 76%, respectively. Aims: We investigated the clinicopathologic characteristics of patients with CRC and their relationship with point mutations of K-ras oncogene codons 12/13 and ras p21 expression. Materials and Methods: K-ras codons 12 and 13 point mutations were examined by direct sequence analysis, whereas the ras p21 expression was evaluated using immunohistochemistry. Results: Statistical analysis of immunohistochemical results showed that the expression of ras p21 was correlated with the advanced age of patients (P = 0.0001), whereas loss of signal was associated with mucinous histotype (P = 0.0001). Mutations in the K-ras gene were detected in 12 of the patients with CRC. Mutations in K-ras gene were found in 12 of 52 tumors (23.07%), and 7 mutations were G-A transitions (58.33% of all mutations), 4 were G-T transversions (33.33%), and only 1 was G-->C transversion (8.33%). A total of 83.33% of the mutation occurred at codon 12 and 16.67% at codon 13. Moreover, K-ras mutations were associated with the sex of patients (P = 0.017). Conclusions: Genetic K-ras alterations were rather low in the Tunisian population, but further study is necessary to unravel the molecular background of CRC.