[824] The Expression of Serum/Glucocorticoid Regulated Kinase 1 (SGK1) and Glucocorticoid Receptor (GR) in Prostatic Tissue

SS Daniel, E Chung, M Tretiakova, S Conzen, H Al-Ahmadie. University of Chicago, Chicago, IL

Background: Prostatic carcinoma (PC) is the most common malignancy in men and the second leading cause of cancer death. Androgens, by regulating the activity of androgen receptor (AR), play a critical role in the development and progression of PC. AR and GR are closely related members of the nuclear hormone receptor superfamily whose role in PC has not been well understood. SGK1, a Ser/Thr protein kinase, was recently identified as an AR-induced gene and is also required for GR-mediated cell survival signaling, but its exact role in PCs has not been explored. We analyzed the expression of AR, SGK1 and GR by immunohistochemistry (IHC) in a cohort of PC patients treated by radical prostatectomy (RP).
Design: Tissue microarrays containing 141 RP specimens with varying Gleason grades were stained by IHC for AR, SGK1 and GR. The stains were assessed semi-quantitatively in both PC and adjacent nonneoplastic prostatic tissue (NP). Any staining was recorded. Intensity was graded on a scale from 0-3 representing negative, weak, moderate and strong, respectively.
Results: Results are summarized in Table 1. All 3 markers exhibited nuclear localization, with SGK1 additionally showing cytoplasmic expression. AR and SGK1 were diffusely expressed in all NP and PC with no significance difference in expression according to Gleason grade. In contrast, GR was detected in 33% of PC and in 65% of NP. In NP, SGK1 and GR were expressed in nuclei of acinar as well as basal cells in varying proportions. Interestingly, SGK1 was uniformly more strongly staining PC compared to NP.

Table 1. Percentage of IHC expression of SGK1, AR, and GR in prostatic tissue
SGK1 (%)AR (%)GR (%)
PC (n =132)132 (100)132 (100)44 (33)
NP (n=138)138 (100)138 (100)90 (65)



Conclusions: Increased SGK1 expression in PC compared to NP suggests a potential role in the development and progression of PC. SGK1 expression is not related to the level of differentiation of PC as determined by Gleason grade. The strong correlation between SGK1 and AR expression supports the hypothesis that AR-mediated induction of SGK1 expression may contribute to the development and progression of PC and offers a potential novel pathway for targeted therapy. Unlike AR and SGK1, GR was not expressed ubiquitously. Therefore, GR may play a role favoring growth in a specific subset of PC.
Category: Genitourinary (including renal tumors)

Wednesday, March 24, 2010 9:30 AM

Poster Session V # 97, Wednesday Morning

 

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