Reevaluation and Identification of the Best Immunohistochemical Panel (pVHL, Maspin, S100P, IMP-3) for Ductal Adenocarcinoma of the Pancreas

CONTEXT: Differentiation of ductal adenocarcinoma of the pancreas from nonneoplastic pancreatic tissues can be challenging, especially in small biopsy and fine-needle aspiration specimens. OBJECTIVE: To investigate the utility of 26 immunohistochemical markers (CAM 5.2, CK cytokeratin 7, CK20, CK17, CK19, MUC1, MUC2, MUC4, MUC5AC, MUC6, p53, DPC4/SMAD4, CDX2, pVHL von Hippel-Lindau tumor suppressor gene protein, S100P, IMP-3 insulin-like growth factor 2 messenger RNA binding protein 3, maspin, mesothelin, claudin 4, claudin 18, annexin A8, fascin, PSCA prostate stem cell antigen, MOC31, CEA carcinoembryonic antigen, and CA19-9 cancer antigen 19-9) in the diagnosis of ductal adenocarcinoma of the pancreas. DESIGN: Immunohistochemical staining for these markers was performed in 60 cases of pancreatic ductal adenocarcinoma on routine and tissue microarray sections. In addition, immunohistochemical staining for maspin, S100P, IMP-3, and pVHL was performed on cell blocks from 67 pancreatic fine-needle aspiration cases, including 44 cases of pancreatic ductal adenocarcinoma. RESULTS: The results demonstrated that (1) more than 90% of cases of ductal adenocarcinoma were positive for maspin, S100P, and IMP-3; (2) nearly all adenocarcinoma cases were negative for pVHL, whereas nonneoplastic ducts and acini were positive for pVHL in all cases; (3) normal/reactive pancreatic ducts were frequently positive for CK7, CK19, MUC1, MUC6, CA19-9, MOC31, PSCA, mesothelin, annexin A8, claudin 4, and claudin 18; (4) normal pancreatic ducts were usually negative for IMP-3, maspin, S100P, CK17, MUC2, MUC4, and MUC5AC; (5) 60% of adenocarcinomas were negative for DPC4/SMAD4; and (6) strong background staining was frequently seen with fascin, PSCA, and annexin A8. CONCLUSIONS: pVHL, maspin, S100P, and IMP-3 constitute the best diagnostic panel of immunomarkers for confirming the diagnosis of pancreatic ductal adenocarcinoma in both surgical and fine-needle aspiration specimens.