Abstract 5324: ERG expression and PTEN loss by BMI and weight change in men with prostate cancer

Background: Obesity and weight gain are associated with poor prostate cancer outcome; underlying mechanisms are unknown. Obesity has been more strongly associated with lethal disease in men positive for the TMPRSS2:ERG gene fusion than negative for this fusion. PTEN loss is associated with increased risk of lethal progression; its association with obesity has not been explored. We evaluated whether prevalence of ERG expression and PTEN loss in prostate tumors differs by BMI and weight change. Methods: From a retrospective cohort study of 1,337 men with clinically-localized prostate cancer who underwent prostatectomy at Johns Hopkins (1993-2006), we sampled 291 men by combination of BMI at 1 year after surgery (normal, overweight, obese) and weight change from 5 years before to 1 year after surgery (loss, maintenance, gain). Within each category, men were frequency-matched on age, Gleason sum, organ confinement, and surgery year. We used genetically validated immunohistochemistry assays to assess ERG positivity and heterogeneous PTEN loss. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of BMI and weight change (adjusted for height, starting weight) with ERG positivity and heterogeneous PTEN loss. Results: Mean age was 56.1 years and mean Gleason sum was 6.2; 73% had organ-confined disease. Prevalence of ERG positivity did not statistically significantly differ by BMI or weight change. However, when jointly categorized by BMI and weight change, overweight/obese men who maintained (OR=2.5; 95%CI 1.1-5.7) or gained weight (OR=2.5; 95%CI 1.1-5.8), and normal weight men who gained weight (OR=4.7; 95%CI 1.4-15.2) were significantly more likely to have ERG positive tumors compared with normal weight men who maintained weight. Overweight/obese men were also significantly more likely (OR=2.4; 95%CI 1.3-4.7) to have PTEN loss compared with normal weight men. When stratified by ERG status, this association appeared to be stronger for men with ERG positive tumors (OR=2.9; 95%CI 1.3-6.8) than for men with ERG negative tumors (OR=1.6; 95%CI 0.6-4.9). Prevalence of PTEN loss did not differ by weight change. When jointly categorized by BMI and weight change, overweight/obese men who maintained (OR=2.0; 95%CI 0.8-5.3) or gained weight (OR=1.9; 95%CI 0.7-5.1) appeared to be more likely to have PTEN loss compared with normal weight men who maintained weight. Conclusions: Overweight/obese men who maintained or gained weight circa diagnosis and normal weight men who gained weight were more likely to have ERG positive tumors. Overweight/obese men were more likely to have tumors with PTEN loss; this association was stronger among overweight/obese men who also had ERG positive tumors. The TMPRSS2:ERG gene fusion and PTEN loss may contribute to the increased risk of poor prostate cancer outcomes among overweight/obese men. Funding: Prostate Cancer Foundation Citation Format: Janelle S. Ho, Ibrahim Kulac, Tamara L. Lotan, John R. Barber, Patrick C. Walsh, Misop Han, Angelo M. De Marzo, Elizabeth A. Platz, Corinne E. Joshu. ERG expression and PTEN loss by BMI and weight change in men with prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5324. doi:10.1158/1538-7445.AM2017-5324