GSTAI expression in normal, preneoplastic, and neoplastic human prostate tissue

Background. Glutathione S-transferases (GSTs), inducible enzymes that catal yze the detoxification of reactive electrophiles and oxidants, protect agai nst neoplastic transformation. Prostatic adenocarcinoma and high-grade pros tatic intraepithelial neoplasia (HGPIN) fail to express GSTP1, a major clas s of GST. This failure of expression is associated with methlyation of the GSTP1 promoter, a somatic alteration proposed to be a critical step in pros tatic carcinogenesis. However, simple atrophy and post-atrophic hyperplasia -proliferative lesions associated with chronic inflammation, which we have termed "proliferative inflammatory atrophy" (PIA)-express elevated levels o f GSTP1 We postulated that this increase in GSTP1 expression in PTA occurs in response to increased oxidative stress. We examined the expression of an other major class of GST, GSTA1 in the human prostate. Methods. We performed immunohistochemistry against GSTA1 on formalin-fixed radical prostatectomies (n=45). A stereological grid point counting method was used to estimate the percent of cells staining positive for GSTA1 in no rmal prostate, PTA, HGPIN, and adenocarcinoma. Results. In contrast to GSTP1, normal peripheral zone epithelium was virtua lly devoid of GSTA1 Strikingly, though, epithelial cells in PIA demonstrate d strong staining for GSTA1 (median of percent of cells staining positive = 44) as compared to those in normal peripheral zone (median=3.0, P<.00001), HGPIN (median=2.9, P<.00001), and adenocarcinoma (median = 3.8, P<.00001). Variations in GSTA1 were also detected between normal anatomic zones: the central zone showed an increase in the percentage of cells staining positiv e (median=20.9) as compared to the transition (median=0.47, P<.0002) and th e peripheral (P<.0001) zones. Conclusions. Expression of GSTA1 is increased in PTA, supporting the concep t that cells within these lesions are subject to localized increases in oxi dative stress. Low levels of GSTA1 and GSTP1 in HGPIN and adenocarcinoma su ggest a broad lack of detoxification activity in these cells, which may be associated with carcinogenesis in the prostate. Prostate 49: 30-37,2001. (C ) 2001 Wiley-Liss, Inc.