Hruban RH, Maitra A, Kern SE, et al. contrast, HPC2 1-B3 immunostained the cytoplasm and luminal surface of all well to moderately differentiated pancreatic ductal adenocarcinomas (16/16). It showed only weak focal staining of poorly differentiated carcinoma. All high grade IPMNs were positive for HPC2 1-B3. Most low to intermediate grade IPMNs were positive (66% of cases). Immunostaining a separate series of pancreatic FNA cell blocks for HPC2 1-B3 showed the relative risk (2.0 [1.23C3.26]) for detecting at least low-grade dysplasia was statistically significant (Fisher Exact test p-value=0.002). Conclusions In order to reduce the mortality of pancreatic cancer, more effective early screening methods are necessary. Our data indicate that a novel monoclonal antibody, HPC2 1-B3, may facilitate the diagnosis of early pancreatic dysplasia. included in the panel data presented in Table 1. Table 1 Screening Panel of Surgically Resected Pancreatic Tissues Immunostained for the HPC2 Antigen using HPC2 1-B3 was significant: RR = 2.0 [1.23C3.26]; p-value = 0.002. In contrast, KOC did not detect low-grade dysplasia and had an overall RR of 1 1.5 [1.13C1.99] and Fisher Exact test p-value = 0.15. Western Blot Analysis and HPC2 1-B3 Secretion Western blot analysis of cultured Panc1 and HeLa tumor cells revealed HPC2 1-B3 protein in both the cell lysates and culture supernatant (Figure 4). Human cervical cancer HeLa cells were chosen because we identified high levels of HPC2 1-B3 protein in this cell line. Our data suggest HPC2 1-B3 is approximately 55C65 kDa in size and is secreted or shed by both tumor cell lines into culture supernatant. Panc1 cells secrete less HPC2 1-B3 than HeLa cells, but together with our immunohistochemical analyses of Misoprostol IPMNs and pancreatic adenocarcinomas (Figures 2 and ?and3),3), this Western blot data support the hypothesis that the HPC2 1-B3 antigen is likely secreted by dysplastic and neoplastic pancreatic ductal cells. Open in a separate window Figure 4 HPC2 1-B3 antigen is a secreted proteinWestern blot analysis demonstrates immunostaining for the HPC2 1-B3 antigen at 55C65 kDa in lystates of both HeLa cells (lane 1) and Panc1 cells (lane 2). HeLa cells express significantly more HPC2 1-B3 antigen than Panc1 cells. Analysis of culture supernatants from HeLa cells (lane 3) reveals the presence of HPC2 1-B3 antigen, suggesting the marker may be secreted by tumor cells. Panc1 secretion (lane 4) is barely detectable (arrow). DISCUSSION In order to reduce the mortality of pancreatic cancer, early screening methods similar to those employed for Misoprostol cervical cancer will be necessary. Our data indicate that a novel monoclonal antibody, HPC2 1-B3, may facilitate the diagnosis of early pancreatic ductal dysplasia, which we suspect could be TM4SF18 more likely to progress to invasive adenocarcinoma. The detection of these early lesions is vital to reducing patient mortality. Pancreatic Ductal Dysplasia Dysplastic pancreatic ductal lesions include IPMNs in the larger ducts and PanINs in the smaller ducts.4,5 Similar to cervical cancer, many cases of pancreatic ductal neoplasia begin as low-grade dysplasia and progress over time into high-grade dysplasia and invasive adenocarcinoma.8C11 Unfortunately, unlike cervical cancer, there are currently no effective screening methods that are both reliable and relatively inexpensive. For example, cytology alone identifies pancreatic ductal adenocarcinoma and high-grade dysplasia, but it often misses low- to intermediate-grade IPMNs. In our experience, a potential pitfall with the cytologic diagnosis of low-grade IPMNs is gastric contamination. EUS-guided FNAs of the body or tail of the pancreas are through the gastric wall, rather than the duodenum. This is significant because duodenal contamination is easily discriminated by the presence of goblet cells in cytologic preparations, but gastric mucosa is morphologically very similar to low-grade IPMNs. Some authors suggest immunohistochemical evaluation of mucin gene expression profiles to address this issue.27C29 Gastric mucosa and duodenal mucosa are negative for HPC2 1-B3 (data not shown). Molecular Markers to Screen for Pancreatic Duct Dysplasia Serological markers for invasive pancreatic cancer are in the early stages of development, but markers12 and radiographic features ofprecancerous lesions are not reliably accurate. 9 Aside from aspirate CEA levels, few immunohistochemical markers have been validated to screen EUS-guided Misoprostol FNAs. For example, in a.