MYC Overexpression at the Protein and mRNA Level and Cancer Outcomes among Men Treated with Radical Prostatectomy for Prostate Cancer.

Andreas Pettersson, Travis Gerke, Kathryn L Penney, Rosina T Lis, Edward C Stack, Nelma Pértega-Gomes, Giorgia Zadra, Svitlana Tyekucheva, Edward L Giovannucci, Lorelei A Mucci, Massimo Loda

Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2019;27(2):201-207

PMID: 29141848

Abstract

The proto-oncogene is implicated in prostate cancer progression. Whether MYC tumor expression at the protein or mRNA level is associated with poorer prognosis has not been well studied. We conducted a cohort study including 634 men from the Physicians' Health Study and Health Professionals Follow-up Study treated with radical prostatectomy for prostate cancer in 1983-2004 and followed up for a median of 13.7 years. MYC protein expression was evaluated using IHC, and we used Cox regression to calculate HRs and 95% confidence intervals (CIs) of its association with lethal prostate cancer (distant metastases/prostate cancer-related death). We assessed the association between MYC mRNA expression and lethal prostate cancer in a case-control study, including 113 lethal cases and 291 indolent controls. MYC nuclear protein expression was present in 97% of tumors. MYC protein expression was positively correlated with tumor proliferation rate ( = 0.37; < 0.001) and negatively correlated with apoptotic count ( = -0.17; < 0.001). There were no significant associations between MYC protein expression and stage, grade, or PSA level at diagnosis. The multivariable HR for lethal prostate cancer among men in the top versus bottom quartile of MYC protein expression was 1.09 (95% CI, 0.50-2.35). There was no significant association between MYC mRNA expression and lethal prostate cancer. Neither MYC protein overexpression nor MYC mRNA overexpression are strong prognostic markers in men treated with radical prostatectomy for prostate cancer. This is the largest study to examine the prognostic role of MYC protein and mRNA expression in prostate cancer. .

©2017 American Association for Cancer Research.

Address: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida.; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.; Department of Oncologic Pathology, Dana-Farber Cancer Institute, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; Departments of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; Department of Oncologic Pathology, Dana-Farber Cancer Institute, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. [email protected].
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