Differential prognosis of replication error phenotype and loss of heterozygosity in sporadic colorectal cancer

Several distinct genetic alterations have been associated with colorectal t umorigenesis. This study investigated the frequency of microsatellite insta bility, also known as replication error (RER), and loss of heterozygosity ( LOH) at six chromosome regions in sporadic colorectal cancer (CRC). Eighty- six tumour and paired normal mucosa samples were included in the study. A p olymerase chain reaction (PCR)-based technique was performed to analyse six (CA)n dinucleotide repeats located near or within regions containing impor tant genes implicated in the complex process of colorectal tumorigenesis (c hromosomes 2p, 3p, 5q, 11p, 17p and 18q). Overall, LOH frequency was higher in RER- tumours (25/46, 54.3%) compared with RER+ tumours (9/40, 22.5) (P= 0.04). To investigate prognostic implications, survival analysis was perfor med for 66 patients. Compared with RER- tumours, patients with RER+ tumours at 2p, 3p, 5q, 11p or 18q were found to have an improved prognosis (overal l survival, P=0.02 and disease-free survival (DFS) P=0.005) this variable b eing an independent prognostic factor by multivariate analysis (P=0.001). O verall survival of patients whose tumours were LOH+ was significantly short er compared with those without LOH (overall survival, P=0.008 and DFS, P=0. 01). Thus, tumours displaying RER+ and LOH+ phenotype, as established by mi crosatellite analysis, show a differential prognosis. These data indicate t hat this may be a useful tool for the identification of patients at differe nt risks affected by CRC. (C) 1999 Published by Elsevier Science Ltd. All r ights reserved.