Glutathione S-transferase: differential expression of alpha, mu, and pi isoenzymes in benign prostate, prostatic intraepithelial neoplasia, and prostatic adenocarcinoma.
Affiliation
Bostwick Laboratories, Glen Allen, VA 23060, USA. bostwick@bostwicklaboratories.comIssue Date
2007-09
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Glutathione S-transferases (GST) comprise a family of enzymes which are critical for inactivation of toxins and carcinogens. We examined the cellular expression of multiple subclasses of GST immunohistochemically in 25 radical prostatectomy specimens with clinically localized prostate cancer. Gleason scores ranged from 5 to 9, and pathologic stages varied from pT2a to pT3b (all N0M0). Antibodies were directed against GST Ya, Yc, and Yk (alpha subclass), Yb1 (micro subclass), and YPr (pi subclass). The percentage of positive cells and intensity of staining was assessed for benign epithelium, high-grade prostatic intraepithelial neoplasia (PIN), and adenocarcinoma. GSTalpha (Ya) was detected in 30% of cells (mean) in benign acini, 4.9% of cells in high-grade PIN, and 4.5% of cells in adenocarcinoma. The corresponding results for alpha (Yk), micro (Yb1), and pi (Yp) were 12.7%, 10.9%, and 3.5%; 8.7%, 5.2%, and 0.6%; and 66.7,% 0%, and 0%, respectively. GST Yc (alpha subclass) displayed the lowest level of expression, with diffuse weak staining in scattered benign secretory cells and only single cells (<1%) in high-grade PIN and carcinoma. These results demonstrate consistent reduction or loss of expression of all subclasses of GST with progression of prostatic neoplasia from benign epithelium to high-grade PIN and carcinoma. We hypothesize that carcinogenesis in the prostate results from impaired cellular handling of mutagenic agents owing to reduction or loss of expression of multiple GST and other detoxifying and antimutagenesis agents.Citation
Glutathione S-transferase: differential expression of alpha, mu, and pi isoenzymes in benign prostate, prostatic intraepithelial neoplasia, and prostatic adenocarcinoma. 2007, 38 (9):1394-401 Hum. Pathol.Journal
Human PathologyDOI
10.1016/j.humpath.2007.02.008PubMed ID
17555796Type
ArticleLanguage
enISSN
0046-8177ae974a485f413a2113503eed53cd6c53
10.1016/j.humpath.2007.02.008