Immunohistochemical expression of pi class glutathione S-transferase in the basal cell layer of benign prostate tissue following chronic treatment with finasteride.

Abstract

Background-Glutathione S-transferases (GST) may prevent carcinogenesis through inactivation of reactive electrophiles by conjugation to reduced glutathione. Treatment directed at the induction or preservation of GST-expression in normal epithelium could have a profound impact on the prevention of prostate neoplasia. Finasteride, a 5--reductase inhibitor, is used as a chemopreventive agent because it blocks the conversion of testosterone to its byproduct which promotes prostate tumour growth. Objective-To investigate GST-expression immunohistochemically in benign prostate tissue from untreated patients and from patients chronically treated with finasteride. Materials-Immunostaining with anti-GST-antibody was performed on 10 (cysto-) prostatectomy, eight simple prostatectomy, and three transurethral prostatectomy specimens. The first set of 10 prostates was from untreated patients operated on for bladder cancer. The other cases were from patients with benign prostatic hyperplasia and chronically treated with finasteride. None of the specimens in either group showed prostatic cancer, prostatic intraepithelial neoplasia, urothelial carcinoma, or chronic prostatitis. Specimens were evaluated for the presence, intensity, and distribution of immunostaining. Results-DiVuse cytoplasmic immunostaining was observed in the basal cell layer of the untreated specimens. Some variability in the expression of GST-was seen within each zone and also between the prostate zones. Only a minority of the secretory cells was stained weakly, mainly in the subnuclear region of the cells facing an uninterrupted basal cell layer. Staining was more homogeneously diVuse in the cytoplasm of the luminal cells facing the basement membrane directly. In the benign epithelium of the finasteride treated specimens the circumferential staining of the basal cells appeared to be more continuous than in the untreated cases, the gaps in the stained basal cell layer being fewer, shorter, or even absent in some ducts and acini. There was no variability in the intensity of staining of the basal cell layer, all the cells being intensely stained in a uniform way. The intensity of staining of the secretory cells was not influenced by finasteride treatment. Conclusions-Following chronic treatment with finasteride the immunohistochemical expression of class glutathione S-transferase in the benign prostate ducts and acini is upregulated in relation to an expanded basal cell layer. This could indicate that finasteride acts as a GSTinducer. (J Clin Pathol 1999;52:350-354)

Glutathione S-transferase: differential expression of α, μ, and π isoenzymes in benign prostate, prostatic intraepithelial neoplasia, and prostatic adenocarcinoma

“…In agreement with other reports [37][38][39][40][41][42][43], we found that GSTp was a reliable marker of basal cells in benign acini. This is similar to the distribution of CuZn-superoxide dismutase, another free radical scavenger [44,45].…”

Expression of pi-class glutathione S-transferase: two populations of high grade prostatic intraepithelial neoplasia with different relations to carcinoma

“…This is in agreement with a previous study by our group. 36 No substantial diVerences were seen between the samples from patients with benign prostatic hyperplasia and those derived from patients unaVected by this disease. Our findings are in agreement with the data derived from a biochemical study performed by Tew et al 35 De Marzo and colleagues 37 proposed that most proliferating cells in normal prostate and benign prostatic hyperplasia tissue reside in the basal cell compartment.…”

“…When basal cells are not present, such as in the gaps present in the basal cell layer, the luminal cells might take up this protective role. 36 It is possible that the early loss of GST-expression in human prostate cells might compromise their electrophilic defences, making them vulnerable to the accumulation of the genetic damage necessary to foster the neoplastic transformation.…”

PTOV1, a novel protein overexpressed in prostate cancer containing a new class of protein homology blocks

“…Many genes and proteins have been reported that show increased levels of expression as a result of neoplastic transformation of prostate cells. Most of these molecules are expressed also in basal epithelial cells in normal prostate (Blok et al, 1995;Reiter et al, 1998;He et al, 1997;Troyer et al, 1995;Montironi et al, 1999;Guate et al, 1997), and thus their expression in tumor cells can be considered a re¯ection either of the expansion of a population of proliferating cells, or the activation in tumor cells of pathways that are operative in normal proliferation. On the other hand, some genes and proteins overexpressed in prostate cancer cells are not expressed, or are not detectable, in normal prostate (Magi Galluzzi et al, 1997;Zhau et al, 1992).…”