Expression of androgen and estrogen related proteins in normal weight and obese prostate cancer patients

• Published in: The Prostate 2009-04, Vol.69 (5), p.520-527
• Main Authors: Gross, Mitchell, Ramirez, Cristina, Luthringer, Daniel, Nepomuceno, Edward, Vollmer, Robin, Burchette, James, Freedland, Stephen J.
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Aged; androgen receptor; Aromatase - metabolism; Biological and medical sciences; Epithelial Cells - metabolism; Epithelial Cells - pathology; estrogen receptor; Estrogen Receptor alpha - metabolism; Estrogen Receptor beta - metabolism; Gynecology. Andrology. Obstetrics; Humans; Male; Male genital diseases; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; obesity; Obesity - metabolism; Prostate - metabolism; Prostate - pathology; prostate cancer; Prostate-Specific Antigen - metabolism; Prostatectomy; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Receptors, Androgen - metabolism; Retrospective Studies; sex steroid axis; Signal Transduction; Stromal Cells - metabolism; Stromal Cells - pathology; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.20901

BACKGROUND Obesity is associated with an aggressive form of prostate cancer and with alterations in androgen and estrogen metabolism. We hypothesized that changes in components of the sex steroid receptor axis may contribute to the clinical aggressiveness of prostate cancer in obese patients. METHODS A database was assembled containing clinical and pathological variables from 539 patients treated with radical prostatectomy at a single urban hospital between 1994 and 2002. Tissue microarrays were constructed from representative patients and expression of androgen receptor (AR), PSA, estrogen receptor α (ERα), estrogen receptor β (ERβ), and aromatase was examined. RESULTS Higher BMI correlated strongly with black race, the presence of extra‐capsular extension, and higher pathologic stage. Expression of AR, PSA, ERβ and aromatase in cancerous epithelial cells did not differ according to obesity status. However, decreased expression of ERα and aromatase was observed in the stromal compartment surrounding non‐cancerous acini in obese patients. CONCLUSION We confirm the previously reported associations between obesity and aggressive clinical and pathologic features in our single‐institution, urban teaching hospital. In comparing obese versus non‐obese patients, there was no difference in expression of androgen or estrogen related proteins in cancerous epithelial cells. However, there was a down‐regulation of ERα and aromatase in the stroma of obese patients. Our data suggest obesity may cause stromal changes in the sex steroid production and signaling pathways which may affect prostate cancer growth via intracrine/paracrine mechanisms. Prostate 69:520–527, 2009. © 2008 Wiley‐Liss, Inc.