Use of IMP3, S100P, and pVHL Immunopanel to Aid in the Interpretation of Bile Duct Biopsies With Atypical Histology or Suspicious for Malignancy

Abstract

Histologic evaluation of an endoscopic bile duct biopsy for malignancy is a known challenge. Our prior study has shown that the insulin-like growth factor-II mRNA binding protein-3 (IMP3), S100P, and the von Hippel-Lindau gene product (pVHL) are a useful immunopanel for the distinction between adenocarcinoma and benign biliary epithelium. To further evaluate the usefulness of the IMP3, S100P, and pVHL immunopanel to aid in the interpretation of bile duct biopsies, 16 histologically challenging bile duct biopsies that exhibited atypical histology or features suspicious for malignancy were immunohistochemically stained for IMP3, S100P, and pVHL. Clinical follow-up data were obtained for each case. The results showed that in the 11 cases that showed adenocarcinoma during follow-up, the following staining patterns in atypical/suspicious cells in the initial biopsies were observed: IMP3-positive/S100P-positive/pVHL-negative or reduced (n=6), IMP3-negative/S100P-positive/pVHL-negative or reduced (n=4), and IMP3-positive/S100P-negative/pVHL-negative (n=1). In the 5 follow-up-proven benign cases, 2 biopsies showed an IMP3-negative/S100P-positive/pVHL-positive pattern in atypical cells and 1 was negative for all 3 proteins. The remaining 2 biopsies exhibited an IMP3-positive/S100P-positive/pVHL-negative or reduced pattern in atypical cells that were histologically considered dysplastic on retrospective review. These observations reaffirm that bile duct adenocarcinoma frequently shows positive IMP3 and/or S100P staining with reciprocal negative or reduced pVHL expression. This staining pattern can also be seen in dysplastic epithelium in the absence of invasive carcinoma. On the contrary, benign biliary epithelium typically lacks IMP3 immunoreactivity and may retain normal pVHL expression. However, caution should be exercised when using this immunopanel in the interpretation of challenging bile duct biopsies, because S100P and pVHL stains may give rise to variable patterns that can be difficult to interpret.

Immunohistochemical distinction between intrahepatic cholangiocarcinoma and pancreatic ductal adenocarcinoma

“…S100P is a member of the S100 calcium-binding protein family, initially isolated from human placenta [17]. Overexpression has been reported in several epithelial cancers including PDA, adenocarcinoma of extrahepatic bile ducts, and gallbladder adenocarcinoma [4,[6][7][8]10,18,19]. Our current findings showed positive S100P staining in 95% of PDA, which was in line with our previous observations [7,9,10].…”

“…We have recently established the diagnostic value of S100P, the von Hippel-Lindau gene product (pVHL), insulin-like growth factor-II messenger RNA-binding protein-3 (IMP3), and mammary serine protease inhibitor (maspin) for PDA, gallbladder adenocarcinoma, and adenocarcinoma of the extrahepatic bile ducts [4][5][6][7][8][9][10]. These studies demonstrated that these biomarkers constitute a useful diagnostic immunohistochemical panel for confirming the diagnosis of adenocarcinoma in difficult cases, which can be helpful in the distinction from normal or reactive epithelium of the pancreas, gallbladder, and extrahepatic bile ducts in surgical, biopsy, and fine-needle aspiration specimens.…”

Diagnostic value of maspin in distinguishing adenocarcinoma from benign biliary epithelium on endoscopic bile duct biopsy

“…In contrast, benign/reactive biliary epithelium frequently exhibits an IMP3-/S100P-/pVHL+ staining pattern [24,25].…”

Practical Immunohistochemistry in Neoplastic Pathology of the Gastrointestinal Tract, Liver, Biliary Tract, and Pancreas

“…167 pVHL immunostaining on bile duct biopsies can be difficult to interpret. In one of our studies, 171 reduced immunoreactivity, instead of completely negative staining, was observed in suspicious cells in one-half of malignant cases. The reduction occurs primarily on cell membranes.…”

“…Nonneoplastic pancreaticobiliary epithelial cells are always negative. However, IMP3 does not discriminate invasive adenocarcinoma from dysplasia, 169,171,178 and thus careful histologic evaluation is still essential. Another disadvantage is that approximately 50% of malignant cases show only focal positivity, which significantly reduces its sensitivity because there may be only rare malignant cells present in a given biopsy.…”