Abstract
BackgroundClaudins are integral membrane proteins that are involved in forming cellular tight junctions. One member of the claudin family, claudin-3, has been shown to be overexpressed in breast, ovarian, and pancreatic cancer. Here we use immunohistochemistry to evaluate its expression in benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN), normal tissue adjacent to prostatic adenocarcinoma (NAC), primary prostatic adenocarcinoma (PCa), and metastatic prostatic adenocarcinoma (Mets).MethodsTissue microarrays were immunohistochemically stained for claudin-3, with the staining intensities subsequently quantified and statistically analyzed using a one-way ANOVA with subsequent Tukey tests for multiple comparisons or a nonparametric equivalent. Fifty-three cases of NAC, 17 cases of BPH, 35 cases of PIN, 107 cases of PCa, and 55 cases of Mets were analyzed in the microarrays.ResultsPCa and Mets had the highest absolute staining for claudin-3. Both had significantly higher staining than BPH (p < 0.05 in both cases) and NAC (p < 0.05 in both cases). PIN had a lower, but non-significant, staining score than PCa and Mets, but a statistically higher score than both BPH and NAC (p < 0.05 for both cases). No significant differences were observed between PCa, Mets, and PIN.ConclusionsTo our knowledge, this represents one of the first studies comparing the immunohistochemical profiles of claudin-3 in PCa and NAC to specimens of PIN, BPH, and Mets. These findings provide further evidence that claudin-3 may serve as an important biomarker for prostate cancer, both primary and metastatic, but does not provide evidence that claudin-3 can be used to predict risk of metastasis.
Highlights
Claudins are integral membrane proteins that are involved in forming cellular tight junctions
No significant differences were seen between prostatic adenocarcinoma (PCa) and metastatic prostatic adenocarcinoma (Mets) or PCa and prostatic intraepithelial neoplasia (PIN) (p > 0.05 in both cases)
In addition to its potential role as a predictive biomarker for cancer, claudin-3 has been shown to bind clostridium perfringens enterotoxin, subsequently leading to toxin-mediated cytolysis, prompting some to suggest that this may indicate a future therapy in select cases of prostate cancer [31,32]. Should such a therapy be developed, the immunohistochemical profiles of patients for this marker may become even more important, as it may serve to guide therapy selection. These results provide a basis for the characterization of claudin-3 staining in both primary prostatic adenocarcinoma and metastatic prostatic adenocarcinoma
Summary
Claudins are integral membrane proteins that are involved in forming cellular tight junctions. Studies conducted before the era of prostate specific antigen (PSA) screening have shown that latent prostate cancer was often diagnosed only after autopsy in older males [2,3,4]. One autopsy study of males over the age of 50, conducted before PSA screening was implemented, indicated that the overall age-adjusted prevalence of latent prostate carcinoma was as high as 34.6% for whites and 36.9% for blacks in the United States [5], providing evidence that not all cases of prostate cancer have the same clinical aggressiveness. Understanding the protein expression patterns associated with prostate adenocarcinoma may provide a new toolset to aid in the diagnosis of prostate cancer, provide prognostic information about the risk of metastasis, and indicate unique treatment targets. Given that the disruption of tight junctions is believed to be one facet of tumorigenesis [14], claudins, one of the transmembrane protein families hypothesized to be the backbone of tight junctions [15], have become a target of focus in the recent cancer literature
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