GSTA1 expression in normal, preneoplastic, and neoplastic human prostate tissue

Authors

  • J. Kellogg Parsons,

    1. The Department of Urology, The Johns Hopkins Medical Institutions, Baltimore, Maryland
    Search for more papers by this author
  • Chad P. Nelson,

    1. The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
    Search for more papers by this author
  • Wesley R. Gage,

    1. The Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, Maryland
    Search for more papers by this author
  • William G. Nelson,

    1. The Department of Urology, The Johns Hopkins Medical Institutions, Baltimore, Maryland
    2. The Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, Maryland
    3. The Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland
    Search for more papers by this author
  • Thomas W. Kensler,

    1. The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
    Search for more papers by this author
  • Angelo M. De Marzo

    Corresponding author
    1. The Department of Urology, The Johns Hopkins Medical Institutions, Baltimore, Maryland
    2. The Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, Maryland
    3. The Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland
    • Department of Pathology, Division of Genitourinary Pathology Bunting/Blaustein Cancer Research Building, Room 153, 1650 Orleans Street, Baltimore, MD 21231-1000.
    Search for more papers by this author

Abstract

BACKGROUND

Glutathione S-transferases (GSTs), inducible enzymes that catalyze the detoxification of reactive electrophiles and oxidants, protect against neoplastic transformation. Prostatic adenocarcinoma and high-grade prostatic intraepithelial neoplasia (HGPIN) fail to express GSTP1, a major class of GST. This failure of expression is associated with methlyation of the GSTP1 promoter, a somatic alteration proposed to be a critical step in prostatic 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 of GSTP1. We postulated that this increase in GSTP1 expression in PIA occurs in response to increased oxidative stress. We examined the expression of another 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 normal prostate, PIA, HGPIN, and adenocarcinoma.

RESULTS

In contrast to GSTP1, normal peripheral zone epithelium was virtually devoid of GSTA1. Strikingly, though, epithelial cells in PIA demonstrated 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 positive (median = 20.9) as compared to the transition (median = 0.47, P < .0002) and the peripheral (P < .0001) zones.

CONCLUSIONS

Expression of GSTA1 is increased in PIA, supporting the concept that cells within these lesions are subject to localized increases in oxidative stress. Low levels of GSTA1 and GSTP1 in HGPIN and adenocarcinoma suggest a broad lack of detoxification activity in these cells, which may be associated with carcinogenesis in the prostate. Prostate 49:30–37, 2001. © 2001 Wiley-Liss, Inc.

Ancillary