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Immunohistochemical study of claudin-4 expression in relation to P504S (AMACR) and their significance in prostatic adenocarcinoma

Ibrahim, Doaa A.a; Mostafa, Naglaa A.a; Abouhashem, Safwat E.b

Egyptian Journal of Pathology: July 2013 - Volume 33 - Issue 1 - p 88–94
doi: 10.1097/01.XEJ.0000429922.48123.a3
Original Articles

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.

Departments of aPathology

bUrology, Faculty of Medicine, Zagazig University, Sharkia, Egypt

Correspondence to Doaa A. Ibrahim, MD, Department of Pathology, Faculty of Medicine, Zagazig University, Sharkia, Egypt Tel: +2001 229 598 864; e-mail:

Received December 4, 2012

Accepted December 20, 2012

©2013Egyptian Journal of Pathology