Genomic instability and alterations in Apc, Mcc and Dcc in Hong Kong patients with colorectal carcinoma

Abstract

Our aim was to reveal the significance of tumor-suppressor genes and genomic instability in 99 Hong Kong Chinese colorectal carcinoma (CRC) patients by PCR-LOH analysis and PCR-PTT assay. The frequencies of allelic loss of Apc, Mcc and Dcc and of APC truncation were 31.3% (15/48), 11.6% (5/43), 44.4% (20/45) and 46/93 (49.5%), respectively. The frequency of Apc LOH was similar to, the Mcc LOH was lower than, and the Dcc LOH was higher than that reported for Caucasians and Japanese. In Hong Kong CRC patients, the replication error-positive (RER+) phenotype occurred with a frequency of 10% (10/99), which was similar to other results using microsatellite markers where RER+ frequencies ranged from 11% to 28%. The rates of genetic alteration in RER+ tumors were lower in tumors harboring p53, Mcc and Dcc alterations; similar in Apc; and higher in Ki-ras tumors compared with RER- tumors, though these differences did not achieve statistical significance. None of the biomarkers examined were predictive of survival independently, but strong trends confirming earlier observations of associations between RER+ phenotypes with proximal tumor location and poorly differentiated tumor status were noted. The RER+ phenotype was correlated significantly to the less aggressive Duke's stage B and improved prognosis. Additionally, tumors with RER+ phenotypes were positively correlated with young age and sex. Our results support the observation that a subset of younger male CRC patients in Hong Kong may develop CRC via the RER pathway and show differences in RER status and sex. A significantly higher percentage of older Hong Kong Chinese CRC patients had APC truncations.