DYSREGULATED EXPRESSION OF CD66A (BGP, C-CAM), AN ADHESION MOLECULE OF THE CEA FAMILY, IN ENDOMETRIAL CANCER

CD66a (BGP, C-CAM) is an adhesion molecule of the carcinoembryonic ant igen family that has been shown to be down-regulated in colorectal, pr ostate, and breast cancers. The purpose of the present study was to de termine its expression pattern in the normal human endometrium and in endometrial neoplasia, For this purpose, we performed immunohistochemi stry using the 4D1/C2 monoclonal antibody on a series of 24 normal end ometrial samples and 47 endometrial carcinomas. Strong CD66a expressio n was observed in glandular and luminal epithelial cells of the normal endometrium with a consistent localization at the apical poles of the se cells throughout the cycle. In late secretory (premenstrual) phase, less of cellular polarity resulted in a membranous expression pattern in some glandular cells. In the analyzed tumor samples increasing are as with a complete loss of expression were observed with increasing ma lignancy grade. The apical expression pattern of the normal epithelium was changed to a membranous all-around pattern in 55% of the tumors, mostly in solid areas. This change correlated with malignancy grade an d could be observed in 3 of 15 G1 tumors, 4 of 12 G2 tumors, 11 of 12 G3 tumors, and 8 of 8 serous-papillary carcinomas. Areas with membrano us expression pattern could be observed along with areas with a normal apical expression pattern in lower grade carcinomas and with areas wi th complete loss of expression in high grade tumors. Northern blot ana lysis showed a loss of mRNA expression in tumor samples and HEC-1B end ometrial adenocarcinoma cells. Loss of protein expression in the tumor samples was also observed by Western blot. In conclusion, CD66a prote in expression is dysregulated in endometrial carcinomas, showing reduc tion or loss of expression with increasing malignancy grade and a chan ge from the apical to a membranous localization.