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Alterations in β‐catenin expression and localization in prostate cancer
Author(s) -
Whitaker Hayley C.,
Girling Joanne,
Warren Anne Y.,
Leung Hing,
Mills Ian G.,
Neal David E.
Publication year - 2008
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20780
Subject(s) - prostate cancer , tissue microarray , prostate , lncap , immunohistochemistry , wnt signaling pathway , pca3 , catenin , cancer research , medicine , cancer , pathology , biology , signal transduction , microbiology and biotechnology
Background Wnt signaling is thought to be important in prostate cancer, in part because proteins such as β‐catenin can also affect androgen receptor signaling. β‐Catenin forms a cell adhesion complex with E‐cadherin raising the possibility that loss of expression or a change in β‐catenin distribution in the cell could also alter downstream signaling, decreased inter‐cellular adhesion and the promotion of metastasis. A number of studies have reported the altered expression and/or localization of β‐catenin as a biomarker in prostate cancer. Methods Tissue microarrays comprised of BPH and low, moderate and high‐grade prostate cancer (n = 77) were assessed for β‐catenin expression and distribution using immunohistochemistry. Staining was also performed on a tissue microarray containing tissue from patients before and after hormone manipulation. The effects of fixation and different antibodies was assessed on fixed LNCaP cell pellets and small prostate tissue microarrays. Results We have observed increased β‐catenin expression in only high Gleason score (>7) prostate cancer. A nuclear re‐distribution of β‐catenin has previously been reported. We noted nuclear β‐catenin in benign prostatic hyperplasia and a gradual loss in nuclear distribution with increasing Gleason grade. We found no evidence for an alteration in β‐catenin expression or re‐distribution with hormone ablation. Altered fixation, antibodies and antibody concentration did affect the intensity and specificity of staining. Conclusions A loss of nuclear β‐catenin is the most consistent feature in prostate cancer rather than absolute levels of expression. We also suggest that variation in immunohistochemical protocols may explain variations in the reported literature. Prostate 68: 1196–1205, 2008. © 2008 Wiley‐Liss, Inc.