Incidence of periprostatic white adipose tissue inflammation in men with prostate cancer.

Abstract

63 Background: Obesity, a common cause of chronic inflammation, is associated with an increased risk of high grade, lethal prostate cancer (PC) and poor outcomes. The existence or clinical importance of periprostatic white adipose tissue inflammation (WATi) in patients (pts) with PC has not been previously described. We examined the relationships among periprostatic WATi and 1) tumor clinicopathologic features, and 2) host factors including age, body mass index (BMI), and circulating metabolic factors. Methods: Periprostatic WAT was collected prospectively from men with PC undergoing radical prostatectomy. WATi was defined by the presence of dead/dying adipocytes surrounded by macrophages forming crown-like structures (CLS). Tumor characteristics and host factors were measured. Wilcoxon rank-sum, Chi-square, or Fisher’s exact tests were used to examine the relationship between WATi and tumor and host characteristics. Results: From 11/2011-8/2015, periprostatic WAT was obtained from 169 pts (median age 62 years, range: 39 -77). Fasting blood samples were collected from 154 pts. CLS were present in 84 (49.7%) of pts. Presence of CLS was associated with higher median BMI (P = 0.02); 40/65 (61.5%) obese pts, 36/83 (43.4 %) overweight pts, and 8/21 (38.1 %) normal weight pts had CLS. Pts with CLS were more likely to have high grade prostate cancer (Gleason grade group IV/V, P = 0.02), larger adipocytes (P = 0.004), and positive surgical margins at the time of surgery (P = 0.04). WATi correlated with higher circulating levels of insulin, triglycerides, and leptin/adiponectin ratio, and lower high density lipoprotein cholesterol, compared to pts without WATi (P’s < 0.05). Conclusions: Periprostatic WATi is common in men with PC. It is associated with high grade PC and alterations in systemic factors that contribute to PC development and progression. Periprostatic WATi may represent a therapeutic target for improving PC risk and outcomes.

Characterization of the effects of 3,3'-diindolylmethane (DIM) in the TRAMP mouse prostate cancer model and DIM's interaction with estrogen receptor signaling

“…Chronic inflammation has been shown to increase the risk of prostate cancer by promoting cell proliferation, angiogenesis and inhibiting apoptosis [116][117][118][119][120]. NF-κB is a transcription factor that regulates genes involved in immune response.…”