Differential Tissue Expression of Androgen and Estrogen Related Proteins in Normal Weight and Obese Prostate Cancer Patients
DJ Luthringer, E Nepomuceno, R Vollmer, J Burchette, SJ Freedland, M Gross. Cedars-Sinai Medical Center, LA, CA; Cedars-Sinai Medical Center, LA, CA; Pathology and Surgery; Duke University Medical Center, Durham, NC
Background: Obesity is associated with an aggressive form of prostate cancer and changes in androgen and estrogen metabolism. Given the associations between obesity, circulating sex sterols and nuclear hormone receptor expression in prostate cancer, we hypothesized that changes in components of the sex steroid receptor axis may contribute to the clinical aggressiveness of prostate cancer in obese patients.
Design: A comprehensive database was assembled containing clinical and pathological variables (age, PSA, ethnicity, body mass index, Gleason score, stage, margin status, etc) from 541 patients (81 obese; 460 non-obese) treated with radical prostatectomy at Cedars-Sinai Medical Center between 1994 and 2002. The final case set selected for study was comprised of 68 obese and 69 non-obese men. Tissue microarrays were constructed from representative case tissue blocks for study by standard immunhistochemical techniques using antibodies against androgen receptor (AR)(Dako clone AR441), PSA (Dako rabbit polyclonal), estrogen receptor (ER)(Ventana Confirm anti-estrogen, SP1), estrogen receptor (ER)(Abcam clone PPG5/10), and aromatase (Santa Cruz Biotechnology CYP19). Semiquantitative analysis was performed, assessing benign and malignant epithelium and the stroma in proximity to each. Statistical analysis was performed.
Results: Body mass index correlated strongly with race, extra-capsular extension, and advanced pathologic stage. PSA, ER and aromatase were expressed in cancerous epithelial cells in most samples. Decreased expression of ER and aromatase in obese patients was observed in the stromal compartment surrounding non-cancerous acini.
Conclusions: 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 ER and aromatase in the stroma of obese patients. Our data suggests obesity may cause stromal changes in sex steroids which can affect prostate cancer growth via intracrine/paracrine mechanisms.
Tuesday, March 10, 2009 9:00 AM
Platform Session: Section G 1, Tuesday Morning