Some of the upregulated genes comprised genes with important functions in the immune response and proliferation, such as claudin 4 (CLDN4), orosomucoid 1 (ORM1), insulin-like growth factor binding protein 2 (IGFBP2), cytochrome P450, family 26, subfamily A, polypeptide 1 (CYP26A1), and growth arrest-specific 1 (GAS1).
We randomly selected the following six upregulated and six downregulated genes from the putative DEGs identified from DON and ZEN treatment groups that were involved in disease or immunity: IGF-1, ORM-1, UBD, SLA-1, HMGCS2, metallothionein 1A (MT1A), nocturnin (NOCT), TRHDE, NNMT, Rho guanine nucleotide exchange factor 6 (ARHGEF6), claudin 4 (CALDN4), and paraoxonase 3 (PON3).
Loss of the tight junction protein claudin 4 correlates with histological growth-pattern and differentiation in advanced gastric adenocarcinoma.
The IHC panels have been updated to include newer antibodies, such as claudin 4. There is some repetition with the 2013 guidelines, but we thought it was important that the reader not have to go back and forth to prior guidelines to determine what antibodies remain useful.
(2) Based on sensitivity and specificity, calretinin (Figure 8, A and B), cytokeratin 5 or 5/6 (Figure 9, A and B), WT1 (Figure 10, A through C), and podoplanin (D2-40) (Figure 11, A and B) are the best positive mesothelioma markers, whereas claudin 4 (Figure 12, A and B), MOC31 (Figure 13, A through C), and BER-EP4 are the best overall carcinoma markers.
(82,83) The markers useful in women include calretinin and possibly, podoplanin (D2-40) (which can also be positive in some cases of PSC) for positive markers in PMM, and claudin 4, MOC31, BG8, and, with less specificity, BER-EP4 for positive adenocarcinoma markers.
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.
Claudin 4 identifies a wide spectrum of epithelial neoplasms and represents a very useful marker for carcinoma versus mesothelioma diagnosis in pleural and peritoneal biopsies and effusions.
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.