THE OVEREXPRESSION OF THE SIALYL-LEWIS(X) MOIETY IS AN INDEPENDENT AND A MORE CONSISTENT MARKER OF COLON CARCINOGENESIS THAN THE OVEREXPRESSION OF C-MYC AND KI-RAS ONCOGENES

The expression of the carbohydrate antigen sialyl-Le(x) and of the oncogenes c-myc and Ki-ras increases after malignant transformation of the colorectum. Since the overexpression of these two oncogenes may affect O- or N-linked carbohydrate chain synthesis, we investigated if this is the case for sialyl-Le(x). In parallel sections from 11 adenomas and 9 colorectal carcinomas Ki-ras and c-myc mRNAs were detected by in situ hybridization and sialyl-Le(x) by immunohistochemistry. The moderate to high overexpression of sialyl-Le(x) found in 64% of adenomas and in 89% of carcinomas is a sharply delineated process, closely related to the local stage of tissue transformation. By contrast, the moderate to high overexpression of c-myc mRNA detected in 27% of adenomas and in 78% of carcinomas affects the whole adenomatous or carcinomatous tissue in a homogeneous manner. The Ki-ras mRNA was moderately and homogeneously overexpressed in 18% of adenomas and in 11% of carcinomas, but its expression level did not differ in adenoma and carcinoma of the same specimen. The independence of the three alterations was confirmed in HT-29 cells and its subclones 16.2 and 15.2, in which the relative amounts of total sialyl-Le(x) epitope were 100%: 67%: 38% while the amounts of c-myc mRNA or Ki-ras mRNA determined by Northern blotting did not vary. These data indicate that in human colon the expression of sialyl-Le(x) is independent from c-myc or Ki-ras oncogenes. It occurs more frequently in the early stage of transformation and is more consistently associated with the malignant process than the overexpression of either oncogene.