Those markers include von Hippel-Lindau tumor suppressor (pVHL), placental S100 (S100P), mammary serine protease inhibitor (maspin), insulin-like growth factor II messenger RNA binding protein-3 (IMP3), mesothelin, prostate stem cell antigen (PSCA), annexin A8, fascin, claudin 4, claudin 18, p53, SMAD family member 4 (DPC4/SMAD4), carcinoembryonic antigen (CEA), cytokeratin (CK) 17, CK19, mucin (MUC) 1, MUC2, MUC5AC, cancer antigen 19-9 (CA19-9), and EPCAM.
In our previous study, (48) we investigated the utility of 26 IHC markers (CAM 5.2, CK7, CK20, CK17, CK19, MUC1, MUC2, MUC4, MUC5AC, MUC6, p53, DPC4/SMAD4, caudal type homeobox 2 [CDX2], pVHL, S100P, IMP3, maspin, mesothelin, claudin 4, claudin 18, annexin A8, fascin, PSCA, EPCAM, CEA, and CA19-9) in 60 cases of pancreatic DADC on tissue microarray and routine tissue sections.
New markers of pancreatic cancer identified through differential gene expression analyses: claudin 18 and annexin A8.
This study investigates the utility of 26 different 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 by using 60 cases of pancreatic DAC on routine and tissue microarray (TMA) sections.
(47) Immunohistochemical staining was performed for these 60 cases of pancreatic DAC (20 conventional tissue sections and 40 TMA sections) and 40 cases of normal/nonneoplastic pancreatic tissues taken from patients with pancreatic carcinoma (20 conventional tissue sections and 20 TMA sections) by using the following markers: (1) epithelial markers (CAM 5.2, CK7, CK20, CK17, CK19); (2) mucin gene products (MUC1, MUC2, MUC4, MUC5AC, MUC6); (3) tumor suppressor genes and transcription factors (p53, DPC4/SMAD4, CDX2, pVHL); and (4) tumor-associated proteins (S100P, IMP-3, maspin, mesothelin, claudin 4, claudin 18, annexin A8, fascin, PSCA, MOC31, CEA, CA19-9).
The results demonstrated that (1) more than 90% of cases were positive for maspin, S100P, and IMP-3; (2) nearly all adenocarcinomas were negative for pVHL, whereas nonneoplastic ducts and acini were strongly positive for pVHL in all cases; (3) normal/reactive pancreatic ducts were positive for CAM 5.2, CK7, CK19, MUC1, MUC6, CA19-9, MOC31, PSCA, mesothelin, an nexin 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 adenocar cinoma cases showed loss of expression of DPC4/SMAD4; and (6) strong background staining was frequently seen with fascin (including staining for endothelial cells and stromal cells), PSCA, and annexin A8.
Pancreatic islet cells were positive for pVHL, IMP-3 (KOC), claudin4, claudin 18, and PSCA, and negative for both CK7 and CK20.