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  • Original Article
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Clinical Research

Periprostatic adipose inflammation is associated with high-grade prostate cancer

Abstract

Background:

Obesity, a cause of subclinical inflammation, is associated with increased risk of high-grade prostate cancer (PC) and poor outcomes. Whether inflammation occurs in periprostatic white adipose tissue (WAT), and contributes to the negative impact of obesity on PC aggressiveness, is unknown.

Methods:

In a single-center, cross-sectional design, men with newly diagnosed PC undergoing radical prostatectomy were eligible for study participation. The primary objective was to examine the prevalence of periprostatic WAT inflammation defined by the presence of crown-like structures (CLS-P) as detected by CD68 immunohistochemistry. Secondary objectives were to explore the clinical and systemic correlates of periprostatic WAT inflammation. Tumor characteristics and host factors including BMI, adipocyte diameter, and circulating levels of lipids, adipokines, and other metabolic factors were measured. Wilcoxon rank-sum, Chi-square, or Fisher’s exact tests, and generalized linear regression were used to examine the association between WAT inflammation and tumor and host characteristics.

Results:

Periprostatic fat was collected from 169 men (median age 62 years; median BMI 28.3). Periprostatic WAT inflammation was identified in 49.7% of patients and associated with higher BMI (P=0.02), larger adipocyte size (P=0.004) and Gleason grade groups IV/V tumors (P=0.02). The relationship between WAT inflammation and high Gleason grade remained significant after adjusting for BMI (P=0.04). WAT inflammation correlated with higher circulating levels of insulin, triglycerides, and leptin/adiponectin ratio, and lower high density lipoprotein cholesterol, compared to those without WAT inflammation (P’s <0.05).

Conclusion:

Periprostatic WAT inflammation is common in this cohort of men with PC and is associated with high-grade PC.

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References

  1. Discacciati A, Orsini N, Wolk A . Body mass index and incidence of localized and advanced prostate cancer—a dose-response meta-analysis of prospective studies. Ann Oncol 2012; 23: 1665–1671.

    Article  CAS  Google Scholar 

  2. Cao Y, Ma J . Body mass index, prostate cancer-specific mortality, and biochemical recurrence: a systematic review and meta-analysis. Cancer Prev Res 2011; 4: 486–501.

    Article  CAS  Google Scholar 

  3. Zhang X, Zhou G, Sun B, Zhao G, Liu D, Sun J et al. Impact of obesity upon prostate cancer-associated mortality: a meta-analysis of 17 cohort studies. Oncol Lett 2015; 9: 1307–1312.

    Article  Google Scholar 

  4. Ribeiro R, Monteiro C, Catalan V, Hu P, Cunha V, Rodriguez A et al. Obesity and prostate cancer: gene expression signature of human periprostatic adipose tissue. BMC Med 2012; 10: 108.

    Article  Google Scholar 

  5. Finley DS, Calvert VS, Inokuchi J, Lau A, Narula N, Petricoin EF et al. Periprostatic adipose tissue as a modulator of prostate cancer aggressiveness. J Urol 2009; 182: 1621–1627.

    Article  CAS  Google Scholar 

  6. Laurent V, Guerard A, Mazerolles C, Le Gonidec S, Toulet A, Nieto L et al. Periprostatic adipocytes act as a driving force for prostate cancer progression in obesity. Nat Commun 2016; 7: 10230.

    Article  CAS  Google Scholar 

  7. Zhang T, Tseng C, Zhang Y, Sirin O, Corn PG, Li-Ning-Tapia EM et al. CXCL1 mediates obesity-associated adipose stromal cell trafficking and function in the tumour microenvironment. Nat Commun 2016; 7: 11674.

    Article  CAS  Google Scholar 

  8. van Roermund JG, Hinnen KA, Tolman CJ, Bol GH, Witjes JA, Bosch JL et al. Periprostatic fat correlates with tumour aggressiveness in prostate cancer patients. BJU Int 2011; 107: 1775–1779.

    Article  Google Scholar 

  9. Woo S, Cho JY, Kim SY, Kim SH . Periprostatic fat thickness on MRI: correlation with Gleason score in prostate cancer. AJR Am J Roentgenol 2015; 204: W43–W47.

    Article  Google Scholar 

  10. Allott EH, Howard LE, Song HJ, Sourbeer KN, Koontz BF, Salama JK et al. Racial differences in adipose tissue distribution and risk of aggressive prostate cancer among men undergoing radiotherapy. Cancer Epidemiol Biomarkers Prev 2014; 23: 2404–2412.

    Article  CAS  Google Scholar 

  11. Olefsky JM, Glass CK . Macrophages, inflammation, and insulin resistance. Annu Rev Physiol 2010; 72: 219–246.

    Article  CAS  Google Scholar 

  12. Iyengar NM, Hudis CA, Dannenberg AJ . Obesity and cancer: local and systemic mechanisms. Ann Rev Med 2015; 66: 297–309.

    Article  CAS  Google Scholar 

  13. Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E, Faloia E et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 2005; 46: 2347–2355.

    Article  CAS  Google Scholar 

  14. Shapiro H, Pecht T, Shaco-Levy R, Harman-Boehm I, Kirshtein B, Kuperman Y et al. Adipose tissue foam cells are present in human obesity. J Clin Endocrinol Metab 2013; 98: 1173–1181.

    Article  CAS  Google Scholar 

  15. Iyengar NM, Zhou XK, Gucalp A, Morris PG, Howe LR, Giri DD et al. Systemic correlates of white adipose tissue inflammation in early-stage breast cancer. Clin Cancer Res 2016; 22: 2283–2289.

    Article  CAS  Google Scholar 

  16. Koru-Sengul T, Santander AM, Miao F, Sanchez LG, Jorda M, Gluck S et al. Breast cancers from black women exhibit higher numbers of immunosuppressive macrophages with proliferative activity and of crown-like structures associated with lower survival compared to non-black Latinas and Caucasians. Breast Cancer Res Treat 2016; 158: 113–126.

    Article  CAS  Google Scholar 

  17. Iyengar NM, Ghossein RA, Morris LG, Zhou XK, Kochhar A, Morris PG et al. White adipose tissue inflammation and cancer-specific survival in patients with squamous cell carcinoma of the oral tongue. Cancer 2016; 122: 3794–3802.

    Article  Google Scholar 

  18. Epstein JI, Zelefsky MJ, Sjoberg DD, Nelson JB, Egevad L, Magi-Galluzzi C et al. A contemporary prostate cancer grading system: a validated alternative to the Gleason score. Eur Urol 2016; 69: 428–435.

    Article  Google Scholar 

  19. Morris PG, Hudis CA, Giri D, Morrow M, Falcone DJ, Zhou XK et al. Inflammation and increased aromatase expression occur in the breast tissue of obese women with breast cancer. Cancer Prev Res 2011; 4: 1021–1029.

    Article  CAS  Google Scholar 

  20. Iyengar NM, Morris PG, Zhou XK, Gucalp A, Giri D, Harbus MD et al. Menopause is a determinant of breast adipose inflammation. Cancer Prev Res 2015; 8: 349–358.

    Article  CAS  Google Scholar 

  21. Subbaramaiah K, Howe LR, Bhardwaj P, Du B, Gravaghi C, Yantiss RK et al. Obesity is associated with inflammation and elevated aromatase expression in the mouse mammary gland. Cancer Prev Res 2011; 4: 329–346.

    Article  CAS  Google Scholar 

  22. Kawasaki N, Asada R, Saito A, Kanemoto S, Imaizumi K . Obesity-induced endoplasmic reticulum stress causes chronic inflammation in adipose tissue. Sci Rep 2012; 2: 799.

    Article  Google Scholar 

  23. Amano SU, Cohen JL, Vangala P, Tencerova M, Nicoloro SM, Yawe JC et al. Local proliferation of macrophages contributes to obesity-associated adipose tissue inflammation. Cell Metab 2014; 19: 162–171.

    Article  CAS  Google Scholar 

  24. Hammarsten J, Hogstedt B . Hyperinsulinaemia: a prospective risk factor for lethal clinical prostate cancer. Eur J Cancer 2005; 41: 2887–2895.

    Article  CAS  Google Scholar 

  25. Cox ME, Gleave ME, Zakikhani M, Bell RH, Piura E, Vickers E et al. Insulin receptor expression by human prostate cancers. Prostate 2009; 69: 33–40.

    Article  CAS  Google Scholar 

  26. Lubik AA, Gunter JH, Hendy SC, Locke JA, Adomat HH, Thompson V et al. Insulin increases de novo steroidogenesis in prostate cancer cells. Cancer Res 2011; 71: 5754–5764.

    Article  CAS  Google Scholar 

  27. Allott EH, Howard LE, Cooperberg MR, Kane CJ, Aronson WJ, Terris MK et al. Serum lipid profile and risk of prostate cancer recurrence: results from the SEARCH database. Cancer Epidemiol Biomarkers Prev 2014; 23: 2349–2356.

    Article  CAS  Google Scholar 

  28. Li H, Stampfer MJ, Mucci L, Rifai N, Qiu W, Kurth T et al. A 25-year prospective study of plasma adiponectin and leptin concentrations and prostate cancer risk and survival. Clin Chem 2010; 56: 34–43.

    Article  CAS  Google Scholar 

  29. Rodriguez C, Freedland SJ, Deka A, Jacobs EJ, McCullough ML, Patel AV et al. Body mass index, weight change, and risk of prostate cancer in the Cancer Prevention Study II Nutrition Cohort. Cancer Epidemiol Biomarkers Prev 2007; 16: 63–69.

    Article  Google Scholar 

  30. Giovannucci E, Rimm EB, Liu Y, Leitzmann M, Wu K, Stampfer MJ et al. Body mass index and risk of prostate cancer in U.S. health professionals. J Natl Cancer Inst 2003; 95: 1240–1244.

    Article  Google Scholar 

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Acknowledgements

We thank all the patients who generously volunteered to participate in this study. This work was supported by the Prostate Cancer Foundation (Movember-Challenge Award), Patricia and William Kleh, and Memorial Sloan Kettering Cancer Center Support Grant/Core Grant (P30 CA008748). LWJ is supported by grants from the National Cancer Institute and Aktiv Against Cancer.

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Correspondence to A J Dannenberg.

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Gucalp, A., Iyengar, N., Zhou, X. et al. Periprostatic adipose inflammation is associated with high-grade prostate cancer. Prostate Cancer Prostatic Dis 20, 418–423 (2017). https://doi.org/10.1038/pcan.2017.31

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