NUCLEAR OVEREXPRESSION OF THE ONCOPROTEIN BETA-CATENIN IN COLORECTAL-CANCER IS LOCALIZED PREDOMINANTLY AT THE INVASION FRONT

Sixty to eighty percent of all colorectal cancers are characterized by mutations in the APC tumor suppressor gene. Recently, it was shown th at these mutations lead to a nuclear overexpression of beta-Catenin by disruption of the wingless/WNT signal pathway. Since nuclear beta-Cat enin functions as a transcriptional activator of hitherto unknown tumo r genes, this form of beta-Catenin is now considered a major oncoprote in in colorectal cancer. Using immunohistochemistry, we investigated t he distribution of overexpressed beta-Catenin within individual colore ctal carcinomas. In the majority of the tumors, we found no homogeneou s staining, but a strong nuclear expression of beta-Catenin predominan tly localized at the invasion front with strongest nuclear staining of isolated, scattered tumor cells. In contrast, cells in the tumor cent er often showed no nuclear staining, but retained a membranous express ion of beta-Catenin, comparable to normal colon epithelium. It is, the refore, likely that in addition to the overexpression of beta-Catenin caused by defects in the APC locus, regulatory events in the tumor its elf lead to a different distribution of this oncoprotein. Possibly, su rrounding tissue at the invasion front can give signals to the tumor c ells, leading to a nuclear translocation of beta-Catenin, where it may play a direct role in tumor invasion processes.