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Tumor expression of adiponectin receptor 2 and lethal prostate cancer.

ABSTRACT: To investigate the role of adiponectin receptor 2 (AdipoR2) in aggressive prostate cancer we used immunohistochemistry to characterize AdipoR2 protein expression in tumor tissue for 866 men with prostate cancer from the Physicians' Health Study and the Health Professionals Follow-up Study. AdipoR2 tumor expression was not associated with measures of obesity, pathological tumor stage or prostate-specific antigen (PSA) at diagnosis. However, AdipoR2 expression was positively associated with proliferation as measured by Ki-67 expression quartiles (P-trend < 0.0001), with expression of fatty acid synthase (P-trend = 0.001), and with two measures of angiogenesis (P-trend < 0.1). An inverse association was observed with apoptosis as assessed by the TUNEL assay (P-trend = 0.006). Using Cox proportional hazards regression and controlling for age at diagnosis, Gleason score, year of diagnosis category, cohort and baseline BMI, we identified a statistically significant trend for the association between quartile of AdipoR2 expression and lethal prostate cancer (P-trend = 0.02). The hazard ratio for lethal prostate cancer for the two highest quartiles, as compared to the two lowest quartiles, of AdipoR2 expression was 1.9 (95% confidence interval [CI]: 1.2-3.0). Results were similar when additionally controlling for categories of PSA at diagnosis and Ki-67 expression quartiles. These results strengthen the evidence for the role of AdipoR2 in prostate cancer progression.

SUBMITTER: Rider JR

PROVIDER: S-EPMC4481603 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Tumor expression of adiponectin receptor 2 and lethal prostate cancer.

Rider Jennifer R JR Fiorentino Michelangelo M Kelly Rachel R Gerke Travis T Jordahl Kristina K Sinnott Jennifer A JA Giovannucci Edward L EL Loda Massimo M Mucci Lorelei A LA Finn Stephen S

Carcinogenesis 20150411 6

To investigate the role of adiponectin receptor 2 (AdipoR2) in aggressive prostate cancer we used immunohistochemistry to characterize AdipoR2 protein expression in tumor tissue for 866 men with prostate cancer from the Physicians' Health Study and the Health Professionals Follow-up Study. AdipoR2 tumor expression was not associated with measures of obesity, pathological tumor stage or prostate-specific antigen (PSA) at diagnosis. However, AdipoR2 expression was positively associated with prolif ...[more]

PMID: 25863129

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Project description:Purpose: Small-cell prostate carcinoma (SCPC) morphology predicts for a distinct clinical behavior, resistance to androgen ablation, and frequent but short responses to chemotherapy. The model systems we report reflect the biology of the human disease and can be used to improve our understanding of SCPC and to develop new therapeutic strategies for it. Experimental Design: We developed a set of CRPC xenografts and examined their fidelity to their human tumors of origin. We compared the expression and genomic profiles of SCPC and large cell neuroendocrine carcinoma (LCNEC) xenografts to those of typical prostate adenocarcinoma xenografts and used a panel of 60 human tumors to validate our findings using immunohistochemistry. Results: We show that SCPC and LCNEC xenograft models retain high fidelity to their human tumors of origin and are characterized by a marked upregulation of UBE2C and other M-phase cell cycle genes in the absence of AR, retinoblastoma (RB1) and cyclin D1 (CCND1) expression and confirm these findings in a panel of CRPC patients’ samples. In addition, array comparative genomic hybridization of the xenografts showed that the SCPC/LCNEC tumors display more copy number variations than the adenocarcinoma counterparts and that there is amplification of the UBE2C locus and microdeletions of RB1 in a subset of these, but no AR nor CCND1 deletions. Moreover, the AR, RB1, and CCND1 promoters showed no CpG methylation in the SCPC xenografts. Conclusion: Modeling human prostate cancer with xenografts allows in-depth and detailed studies of its underlying biology. The detailed clinical annotation of the donor tumors enables associations of anticipated relevance to be made. Futures studies in the xenografts will address the functional significance of the findings. 22 samples were analysed, that included MDA PCa 79 (n = 3), 117-9 (n = 3), 130 (n = 2), 144-4 (n = 4), 144-13 (n = 5), 146-10 (n = 3), 155-2 (n = 1), and 155-12 (n = 1). MDA PCA 79, 117-9 and 130 samples had the pathologic characteristics of prostate adenocarcinoma and were compared against MDA PCA 144-4, 144-13, 146-10 and 155-12 that have the pathologic features of prostate small cell/ large cell neuroendocrine carcinoma

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Tumor expression of adiponectin receptor 2 and lethal prostate cancer.

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Tumor expression of adiponectin receptor 2 and lethal prostate cancer.

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