ALLELIC LOSSES ASSOCIATED WITH THE METASTATIC POTENTIAL OF COLORECTAL-CARCINOMA

The aim of this study was to define the association of allelic losses with the metastatic potential of colorectal carcinoma and to determine whether allelic losses can be genetic markers for the prognosis of pa tients with colorectal carcinoma. Eighty primary colorectal tumors and 31 liver metastases from 95 patients were examined for loss of hetero zygosity (LOH) at the APC, p53, RB, DCC and chromosome 14q loci by usi ng polymerase chain reaction-single strand conformation polymorphism a nalysis and restriction fragment length polymorphism analysis. The inc idence of LOH at the DCC and RB loci and on chromosome 14q in liver me tastases was significantly higher than that in primary tumors. DCC and RB alterations were detected more frequently in primary tumors with h igher metastatic potential. Although no statistically significant asso ciation was found between these losses and survival or distant metasta sis, patients with DCC losses showed poorer survival by multivariate a nalysis (p=0.056). Thus, inactivation of the DCC and RB genes and gene (s) on chromosome 14q seem to be critical genetic events for the acqui sition of metastatic potential in colorectal carcinoma. However, furth er studies will be required to utilize these genetic alterations as va luable prognostic markers.