[832] Overexpression of the Soluble Epoxide Hydrolase in Human Prostate Adenocarcinoma with a Downregulation Following Androgen Deprivation Therapy

Xianzhong Ding, Jie Liao, Haonan Li, Jiaoti Huang, Guang-Yu Yang. Northwestern University Feinberg School of Medicine, Chicago, IL; David Geffen School of Medicine at UCLA, Los Angeles, CA

Background: Soluble epoxide hydrolase (sEH) is a bifunctional enzyme with C-terminal hydrolase and N-terminal phosphatase activities. The C-terminal hydrolase converts anti-inflammatory epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids (DHETs). The phosphatase activity involves cholesterol and androgen metabolism. sEH gene deficient mice shows dysregulated circulating testosterone levels. However, little is known if this bifunctional enzyme involves in prostate carcinogenesis.
Design: Prostate specimens were collected from 75 patients with prostatectomy including benign and malignant tissues. Additional 26 prostate cancer specimens with androgen deprivation therapy were also selected. 95% (71/75) prostate cancer in this study has Gleason score 7. A high-throughput tissue microarray (TMA) was constructed for these specimens. Immunohistochemistry was carried out using Rabbit specific anti-sEH antibody and Avidin-biotin-peroxidase approaches. The proper positive and negative controls were also established. Based on the staining intensity, the staining of the prostate tissues was classified as no staining (0), low intensity (+), moderate intensity (++) or high intensity staining (+++).
Results: Distinct over-expression of sEH was identified in prostate adenocarcinoma compared to normal and benign atrophic prostate. 72% (49/69) prostatic adenocarcinoma showed diffuse moderate to strong positive staining for sEH. The positive staining was specifically identified in the cytoplasm. In contrast, 71% (52/73) normal and 94% (17/18) benign atrophic prostate epithelium were negative or weakly positive for sEH. In 26 cases of hormone-treated cancer, a significant decrease of staining intensity of sEH was observed with only 38% (10/26) cancers displaying moderate to strong positivity (38% versus 72% in non-treated cancer, p<0.05).


Conclusions: This study has clearly demonstrated an over-expression of sEH in prostate adenocarcinoma. Its expression was markedly down-regulated following androgen deprivation therapy. This study warrants further exploring the role of sEH in prostate carcinogenesis.
Category: Genitourinary (including renal tumors)

Tuesday, March 20, 2012 1:00 PM

Poster Session IV # 101, Tuesday Afternoon

 

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