HER-2 NEU EXPRESSION IN PANCREATIC ADENOCARCINOMA - RELATION TO TUMORDIFFERENTIATION AND SURVIVAL/

HER-2/neu expression in pancreatic adenocarcinoma has been inconsisten tly reported and has not been fully evaluated with respect to histolog ic grade and tumor grade heterogeneity. We studied HER-2/neu expressio n in a series of 79 primary pancreatic carcinomas using immunohistoche mical methods, with expression scored for each histologic grade repres ented in each tumor. We found significantly lower expression of HER-2/ neu in poorly differentiated (PD) portions of tumors-those areas lacki ng glandular differentiation-compared to well-differentiated (WD) and moderately differentiated (MD) portions of tumors. Forty-two of 68 (62 %) invasive tumors with WD or MD glands showed moderate or strong expr ession of HER-2/neu in WD/MD areas; only 6 of 32 (19%) invasive tumors with PD areas showed similar expression in PD. In mutually exclusive patient sets, we also found a statistically different prevalence of HE R-2/neu expression in patients with PD (6/32 cases; 19%) and without P D (29/47 cases; 62%) tumors (p < 0.001). Twenty-three cases had direct ly comparable areas of PD versus MD or WD. In 19 of 23 cases HER-2/neu expression was graded comparatively lower (or negative) in areas of P D than in MD or WD. Overall 46 of 79 cases (58%) showed moderate to st rong HER-2/neu expression inclusive of all histologic grades, and 63 o f 79 (80%) cases were HER-2/neu positive, if including weak or focal s taining. There was no significant difference in the survival of patien ts with HER-2/neu-positive versus -negative tumors or in patients with versus without PD tumors. We have confirmed that although HER-2/neu g ene expression is common to many pancreatic carcinomas, it is not comm on to tumors lacking glandular differentiation. HER-2/neu gene express ion could not be related to survival differences-perhaps due to overal l poor survival within adenocarcinomas of the pancreas-but the pattern of HER-2/neu expression suggests a relationship to glandular differen tiation and early oncogenesis.