Abstracts
2001 Digestive Disease Week

# 563 Increased Frequency of Heparanase Gene Expression in Human Primary and Metastatic Pancreatic Cancer
Anthony W. Kim, Xiulong Xu, Paolo Gattuso, Richard A. Prinz, Chicago, IL

INTRODUCTION: Extracellular matrix (ECM) degradation is an essential step that allows tumor cells to penetrate a tissue barrier and become metastatic. Heparanase (HPR) is an endoglycosidase that specifically degrades the heparan sulfate of proteoglycan, a chief component of the ECM. Previous studies demonstrated that HPR expression could be detected in hepatocellular, breast, and colon carcinomas. This study tests whether HPR is expressed in pancreatic cancer.

METHODS: 82 pancreatic tumor samples and 7 normal pancreas samples collected from surgical specimens were examined for HPR gene expression by in situ hybridization with an antisense RNA probe. Tumors included 70 adenocarcinomas and twelve metastases from adenocarcinomas. The metastases included three implants on the small intestine, three on the peritoneum, two on the gallbladder, one on the spleen, one on the stomach, and one on the thigh. Two primary adenocarcinomas known to be positive by in situ hybridization were additionally immunostained using immunofluorescent techniques. HPR expression was compared with the clinicopathological features of the pancreatic cancers.

RESULTS: The percentage of HPR expression in pancreatic adenocarcinoma and its metastases was 72% (59/82). 50 of 70 primary pancreatic adenocarcinomas (71%) and 9 of the 12 metastases (75%) were HPR positive. Neither age nor gender was a predictor of HPR expression. Neither tumor stage nor lymph node involvement were independent predictors of HPR expression. None of the 7 normal pancreas specimens were HPR positive. Both specimens that were HPR positive on immunofluorescence were also positive when studied by in situ hybridization.

CONCLUSION: HPR is expressed with high frequency in pancreatic adenocarcinoma and its metastases, but not in normal pancreatic tissue. HPR may contribute to the highly invasive and early metastatic characteristics of pancreatic cancer. HPR expression appears to be independent of age, gender, tumor stage, and lymph node involvement.