LOSS OF MEMBRANOUS E-CADHERIN EXPRESSION IN PANCREATIC-CANCER - CORRELATION WITH LYMPH-NODE METASTASIS, HIGH-GRADE, AND ADVANCED-STAGE

Epithelial cadherin (E-cadherin) is a Ca2+-dependent cell-cell adhesio n molecule that connects cells via homotypic interactions. Its functio n is critical in the induction and maintenance of cell polarity and di fferentiation, and its loss of downregulation is associated with an in vasive and poorly differentiated phenotype in colon and other tumours. We have used an avidin-biotin immunoperoxidase technique to localize E-cadherin in microwave-treated, paraffin-embedded sections from 36 pa tients with pancreatic adenocarcinomas. E-cadherin was expressed by no rmal ductal and acinar cells with typical membranous staining at the i ntercellular junctions. Loss of normal surface E-cadherin expression w as found in 19/36 (53 per cent) tumours compared to the adjacent norma l ductal cells. Abnormal E-cadherin expression was found more frequent ly in poorly differentiated (grade III) (6/7, 86 per cent) than in wel l-differentiated tumours (grade I) (4/14, 28 per cent) (P=0.012). Memb ranous E-cadherin expression was also lost more frequently in primary tumours with lymph node (stage III) (14/23, 61 per cent) and distant m etastasis (stage TV) (2/2, 100 per cent) compared with 3/11 (27 per ce nt) lymph node-negative tumours (stage I) (P=0.043). In conclusions, o ur data indicate that loss of membranous E-cadherin expression is asso ciated with high grade and advanced stage in pancreatic cancer.