Objectives: Claudins are a family of ∼24 tight junction proteins that are frequently altered in several human cancers. The aim of this study was to evaluate the expression and the prognostic relevance of claudin-4 in relation to P504S [α-methylacyl-CoA racemase (AMACR)] in benign, preneoplastic, and neoplastic prostate tissue samples.
Materials and methods: Immunohistochemical analysis was carried out to determine expression levels of claudin-4 and AMACR protein as markers for prostatic adenocarcinoma (PCa; n=40), prostatic intraepithelial neoplasia (PIN; n=26), and benign prostatic hyperplasia (BPH; n=10). The relationship between the expression of these proteins and clinicopathological parameters such as Gleason’s score, pathological stage, prostate-specific antigen value, and patients’ age was studied.
Results: A significant increase in claudin-4 expression was observed from BPH through low-grade and high-grade PIN to primary PCa (40, 50, 75, and 85%, respectively; P=0.013). PCa had the highest mean staining score for claudin-4 (P=0.0008), which was significant. P504S showed positive expression in 90% of PCas, 87.5% of high-grade PINs, and 70% of low-grade PINs. Ninety percent of the patients with BPH did not show P504S expression. PCa had the highest mean staining score for P504S (P=0.00004), which was significant. Low expression of claudin-4 was associated with a Gleason score of 7 or higher (P=0.035) and a high prostate-specific antigen value (>10 ng/ml; P=0.021). Claudin-4 expression increased with pT-stage but with no significant difference. P504S did not show a significant relationship with any of the clinicopathological parameters. A highly significant association was found between P504S and claudin-4 expression (P<0.001).
Conclusion: Our results suggest that a combination of AMACR and claudin-4 may be of great value in increasing the diagnostic accuracy for PCa. Moreover, claudin-4 may serve as an important biomarker for and a promising target for antibody-based therapy of prostate cancer.