Immunohistochemical profiles of claudin-3 in primary and metastatic prostatic adenocarcinoma. Diagn Pathol 6:12

University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Diagnostic Pathology (Impact Factor: 2.6). 01/2011; 6(1):12. DOI: 10.1186/1746-1596-6-12
Source: PubMed


Claudins 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).
Tissue 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.
PCa 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.
To 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.

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Available from: Anil V Parwani
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    • "Figure 4 reports the expression scatter plots of the two markers with the strongest overexpression in cancer (alpha-methylacyl-CoA racemase/AMACR [44] and CLDN3 [43]) and in normal (FLNC [42] and keratin 5/KRT5 [45]) tissue and KLK3/PSA for comparison. The new markers do not appear to be clearly superior to KLK3/PSA inasmuch as their expression is not drastically different in normal and cancerous tissues and their expression in normal and cancer tissues varies widely not allowing for the classification of single patients according to the expression levels, although the expression differences are statistically significant. "
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    ABSTRACT: Biomarkers are important for early detection of cancer, prognosis, response prediction, and detection of residual or relapsing disease. Special attention has been given to diagnostic markers for prostate cancer since it is thought that early detection and surgery might reduce prostate cancer-specific mortality. The use of prostate-specific antigen, PSA (KLK3), has been debated on the base of cohort studies that show that its use in preventive screenings only marginally influences mortality from prostate cancer. Many groups have identified alternative or additional markers, among which PCA3, in order to detect early prostate cancer through screening, to distinguish potentially lethal from indolent prostate cancers, and to guide the treatment decision. The large number of markers proposed has led us to the present study in which we analyze these indicators for their diagnostic and prognostic potential using publicly available genomic data. We identified 380 markers from literature analysis on 20,000 articles on prostate cancer markers. The most interesting ones appeared to be claudin 3 (CLDN3) and alpha-methysacyl-CoA racemase highly expressed in prostate cancer and filamin C (FLNC) and keratin 5 with highest expression in normal prostate tissue. None of the markers proposed can compete with PSA for tissue specificity. The indicators proposed generally show a great variability of expression in normal and tumor tissue or are expressed at similar levels in other tissues. Those proposed as prognostic markers distinguish cases with marginally different risk of progression and appear to have a clinically limited use. We used data sets sampling 152 prostate tissues, data sets with 281 prostate cancers analyzed by microarray analysis and a study of integrated genomics on 218 cases to develop a multigene score. A multivariate model that combines several indicators increases the discrimination power but does not add impressively to the information obtained from Gleason scoring. This analysis of 10 years of marker research suggests that diagnostic and prognostic testing is more difficult in prostate cancer than in other neoplasms and that we must continue to search for better candidates. Electronic supplementary material The online version of this article (doi:10.1007/s10555-013-9470-4) contains supplementary material, which is available to authorized users.
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    ABSTRACT: Tight junctions (TJs) mediate cell-cell adhesion between epithelial cells, maintain cell polarity and regulate the paracellular transit of ions and molecules. Epithelial cells in order to become cancerous disassemble their TJs. Although many TJ proteins are down-regulated during cell transformation, others are in contrast overexpressed. The case is particularly relevant for claudins, where not only each tissue, but each tumor within a given organ expresses a specific set of claudins. In this chapter we will explain how the expression of TJ proteins in cancerous cells, has been used as a molecular tool to identify tumors and predict patient survival rates. In addition we will describe novel strategies that target TJ proteins for cancer treatment and to enhance the delivery of therapeutic drugs through the paracellular pathway of tumors.
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