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

TitleMYC Overexpression at the Protein and mRNA Level and Cancer Outcomes among Men Treated with Radical Prostatectomy for Prostate Cancer.
Publication TypeJournal Article
Year of Publication2018
AuthorsPettersson A, Gerke T, Penney KL, Lis RT, Stack EC, Pertega-Gomes N, Zadra G, Tyekucheva S, Giovannucci EL, Mucci LA, Loda M
JournalCancer Epidemiol Biomarkers Prev
Volume27
Issue2
Pagination201-207
Date Published2018 02
ISSN1538-7755
KeywordsAdult, Aged, Biomarkers, Tumor, Follow-Up Studies, Genes, myc, Humans, Male, Middle Aged, Prospective Studies, Prostatectomy, Prostatic Neoplasms, Proto-Oncogene Proteins c-myc, RNA, Messenger
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. .

DOI10.1158/1055-9965.EPI-17-0637
Alternate JournalCancer Epidemiol Biomarkers Prev
PubMed ID29141848
PubMed Central IDPMC5831163
Grant ListP50 CA090381 / CA / NCI NIH HHS / United States
L30 CA130716 / CA / NCI NIH HHS / United States
P01 CA087969 / CA / NCI NIH HHS / United States
R01 CA187918 / CA / NCI NIH HHS / United States
U01 CA167552 / CA / NCI NIH HHS / United States
R01 CA131945 / CA / NCI NIH HHS / United States
R01 CA034944-03 / CA / NCI NIH HHS / United States
R01 HL034595-07 / HL / NHLBI NIH HHS / United States
R01 CA040360 / CA / NCI NIH HHS / United States
R01 HL026490-03 / HL / NHLBI NIH HHS / United States
R01 CA097193 / CA / NCI NIH HHS / United States
R01 CA141298 / CA / NCI NIH HHS / United States
Related Faculty: 
Massimo Loda, M.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700