IMP3 Expression Can Distinguish Cholangiocarcinomas and Metastatic Pancreactic Ductal Carcinomas from Benign Bile Duct Lesions
DG Wagner, Q Yang, LA McMahon, BO Spaulding, HL Wang, H Xu. University of Rochester Medical Center, Rochester; Dako North America, Carpinteria; Cedars-Sinai Medical Center, Los Angeles
Background: Insulin growth factor (IGF) messenger RNA binding protein 3 (IMP3), also known KOC and L523S, is expressed during embryogenesis and in malignancies. It functions to promote tumor cell proliferation by enhancing IGF-II protein expression. IMP3 expression in cholangiocarcinoma and pancreatic ductal carcinoma has been reported, but its diagnostic value in segregating these two types of malignancy from benign ductal lesions has not been investigated.
Design: Surgically resected or biopsied cholangiocarcinomas (intrahepatic, n=41; extrahepatic, n=4), metastatic pancreatic ductal carcinomas in the liver (n =4), pancreatic ductal carcinomas (n=20), bile duct adenomas (intrahepatic, n=5; extrahepatic, n=2) and bile duct hamartomas (n=11) were immunohistochemically studied using a monoclonal antibody against IMP3 (Dako). Cytoplasmic staining was considered positive. The percentage of positively stained tumor cells was recorded and the staining intensity was graded as weak, moderate or strong. A p value of <0.05, as determined by two-tailed Fisher exact test, was considered statistically significant.
Results: Thirty-nine of 45 (87%) cholangiocarcinomas were positive for IMP3, among which 35 cases showed moderate or strong cytoplasmic staining in >90% of tumor cells and 4 cases exhibited weak to moderate staining in 40-50% of tumor cells. Three of 4 (75%) metastatic pancreatic ductal carcinomas showed strong cytoplasmic staining in >90% of tumor cells. Of 20 pancreatic ductal carcinomas, 15 (75%) were moderately to strongly positive for IMP3 in >90% of tumor cells, and the remaining 5 cases showed a variable degree of cytoplasmic staining in 10-50% of tumor cells. IMP3 expression was not significantly different among these groups. In contrast, no IMP3 expression was detected in any of 7 bile duct adenomas or 11 bile duct hamartomas. The non-neoplastic bile ducts or ductules in tumor sections were also completely negative for IMP3 expression.
Conclusions: A large proportion of cholangiocarcinomas and metastatic or primary pancreatic ductal carcinomas highly expressed IMP3 but benign biliary lesions did not. These findings indicate that immunohistochemical detection of IMP3 expression can be utilized to distinguish benign bile ductal lesions from malignant pancreaticobiliary carcinomas, in particular when limited material from a needle core biopsy is evaluated.
Category: Liver & Pancreas
Tuesday, March 10, 2009 2:15 PM
Platform Session: Section E, Tuesday Afternoon