title: 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.
authors: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA, rider@hsph.harvard.edu.
authors: Jennifer R
authors: JR
authors: Rider
authors: Pathology Unit, Addarii Institute of Oncology, S. Orsola-Malphighi Hospital, 40126 Bologna, Italy.
authors: Michelangelo
authors: M
authors: Fiorentino
authors: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA, Pathology Unit, Addarii Institute of Oncology, S. Orsola-Malphighi Hospital, 40126 Bologna, Italy, Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA, Department of Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA and Department of Pathology, Trinity College Dublin, Dublin 8, Ireland.
authors: Rachel
authors: R
authors: Kelly
authors: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA, Pathology Unit, Addarii Institute of Oncology, S. Orsola-Malphighi Hospital, 40126 Bologna, Italy, Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA, Department of Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA and Department of Pathology, Trinity College Dublin, Dublin 8, Ireland.
authors: Travis
authors: T
authors: Gerke
authors: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA, Pathology Unit, Addarii Institute of Oncology, S. Orsola-Malphighi Hospital, 40126 Bologna, Italy, Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA, Department of Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA and Department of Pathology, Trinity College Dublin, Dublin 8, Ireland.
authors: Kristina
authors: K
authors: Jordahl
authors: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA, Pathology Unit, Addarii Institute of Oncology, S. Orsola-Malphighi Hospital, 40126 Bologna, Italy, Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA, Department of Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA and Department of Pathology, Trinity College Dublin, Dublin 8, Ireland.
authors: Jennifer A
authors: JA
authors: Sinnott
authors: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
authors: Edward L
authors: EL
authors: Giovannucci
authors: Department of Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA and.
authors: Massimo
authors: M
authors: Loda
authors: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors: Lorelei A
authors: LA
authors: Mucci
authors: Department of Pathology, Trinity College Dublin, Dublin 8, Ireland.
authors: Stephen
authors: S
authors: Finn
mesh_terms: D052242:Adiponectin / Q000097:blood; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D014408:Biomarkers, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D054890:Fatty Acid Synthase, Type I / Q000096:biosynthesis*; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D009765:Obesity / Q000150:complications; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000401:mortality* / Q000473:pathology*; D054419:Receptors, Adiponectin / Q000096:biosynthesis*
chemical_list: C475420:ADIPOR2 protein, human; D052242:Adiponectin; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D054419:Receptors, Adiponectin; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I; D017430:Prostate-Specific Antigen