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 patients with colorectal carcinoma. Eighty primary colorectal tumors and 31 liver metastases from 95 patients were examined for loss of heterozygosity (LOH) at the APC, p53, RB, DCC and chromosome 14q loci by using polymerase chain reaction-single strand conformation polymorphism analysis and restriction fragment length polymorphism analysis. The incidence of LOH at the DCC and RB loci and on chromosome 14q in liver metastases was significantly higher than that in primary tumors. DCC and RB alterations were detected more frequently in primary tumors with higher metastatic potential. Although no statistically significant association was found between these losses and survival or distant metastasis, patients with DCC losses showed poorer survival by multivariate analysis (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 acquisition of metastatic potential in colorectal carcinoma. However, further studies will be required to utilize these genetic alterations as valuable prognostic markers.