Serum/glucocorticoid-regulated kinase 1 expression in primary human prostate cancers

Abstract

Background: Serum/glucocorticoid-regulated kinase 1 (SGK1), a known target of the androgen receptor (AR) and glucocorticoid receptor (GR), is reported to enhance cell survival. This study sought to better define the role of SGK1 and GR in prostate cancer.

Methods: Immunohistochemistry was performed for AR, GR, and SGK1 on primary prostate cancers (n = 138) and 18 prostate cancers from patients treated with androgen deprivation therapy. Relative staining intensity was compared utilizing a Fisher's exact test. Univariate analyses were performed using log-rank and chi-squared tests to evaluate prostate cancer recurrence with respect to SGK1 expression.

Results: SGK1 expression was strong (3+) in 79% of untreated cancers versus 44% in androgen-deprived cancers (P = 0.003). Conversely, GR expression was present in a higher proportion of androgen-deprived versus untreated cancers (78% vs. 38%, P = 0.002). High-grade cancers were nearly twice as likely to have relatively low (0 to 2+) SGK1 staining compared to low-grade cancers (13.8% vs. 26.5%, P = 0.08). Low SGK1 expression in untreated tumors was associated with increased risk of cancer recurrence (adjusted log-rank test P = 0.077), 5-year progression-free survival 47.8% versus 72.6% (P = 0.034).

Conclusions: SGK1 expression is high in most untreated prostate cancers and declines with androgen deprivation. However, these data suggest that relatively low expression of SGK1 is associated with higher tumor grade and increased cancer recurrence, and is a potential indicator of aberrant AR signaling in these tumors. GR expression increased with androgen deprivation, potentially providing a mechanism for the maintenance of androgen pathway signaling in these tumors. Further study of the AR/GR/SGK1 network in castration resistance.

Copyright © 2011 Wiley Periodicals, Inc.

Figures

Fig. 1

Immunohistochemical analysis of prostate cancer tissue. A: SGK1 expression. Representative pictures showing SGK1 expression is increased in prostate cancercell scompared to benign surrounding epithelium (1 stpanel-20 μ magnification, black lineis drawn to show demarcation of cancerous area).In TN-PC (middle two panels) SGK1 expression is variable. In AD-PC, high SGK1 expression was less frequent (40×). B: GR was expressed in a higher percentage of AD-PC compared to TN-PC (40×).C: AR expression was universally positive and pre dominantly nuclear in both TN-PC and AD-PC(40×).

Fig. 2

PSA progression free survival estimates. Kaplan–Meier log-rank survival estimates of progression-free survival for (A). All patients (B). Stratified by Gleason grade low (5–6) versus intermediate/high (7–9). C: Stratified by SGK1 expression high (3+) versus low (0 to 2+).