Title | A Prospective Investigation of PTEN Loss and ERG Expression in Lethal Prostate Cancer. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Ahearn TU, Pettersson A, Ebot EM, Gerke T, Graff RE, Morais CL, Hicks JL, Wilson KM, Rider JR, Sesso HD, Fiorentino M, Flavin R, Finn S, Giovannucci EL, Loda M, Stampfer MJ, De Marzo AM, Mucci LA, Lotan TL |
Journal | J Natl Cancer Inst |
Volume | 108 |
Issue | 2 |
Date Published | 2016 Feb |
ISSN | 1460-2105 |
Keywords | Age Factors, Aged, Biomarkers, Tumor, Body Mass Index, Disease Progression, Follow-Up Studies, Gene Expression Regulation, Neoplastic, Health Personnel, Humans, Immunohistochemistry, Kaplan-Meier Estimate, Male, Neoplasm Grading, Neoplasm Staging, Odds Ratio, Oncogene Proteins, Fusion, Physicians, Proportional Hazards Models, Prospective Studies, Prostatic Neoplasms, PTEN Phosphohydrolase, Risk Assessment, Serine Endopeptidases, Trans-Activators, Transcriptional Regulator ERG, Tumor Suppressor Proteins, United States |
Abstract | BACKGROUND: PTEN is a tumor suppressor frequently deleted in prostate cancer that may be a useful prognostic biomarker. However, the association of PTEN loss with lethal disease has not been tested in a large, predominantly surgically treated cohort. METHODS: In the Health Professionals Follow-up Study and Physicians' Health Study, we followed 1044 incident prostate cancer cases diagnosed between 1986 and 2009 for cancer-specific and all-cause mortality. A genetically validated PTEN immunohistochemistry (IHC) assay was performed on tissue microarrays (TMAs). TMPRSS2:ERG status was previously assessed in a subset of cases by a genetically validated IHC assay for ERG. Cox proportional hazards models adjusting for age and body mass index at diagnosis, Gleason grade, and clinical or pathologic TNM stage were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association with lethal disease. All statistical tests were two-sided. RESULTS: On average, men were followed 11.7 years, during which there were 81 lethal events. Sixteen percent of cases had complete PTEN loss in all TMA cores and 9% had heterogeneous PTEN loss across cores. After adjustment for clinical-pathologic variables, complete PTEN loss was associated with lethal progression (HR = 1.8, 95% CI = 1.2 to 2.9). The association of PTEN loss (complete or heterogeneous) with lethal progression was only among men with ERG-negative (HR = 3.1, 95% CI = 1.7 to 5.7) but not ERG-positive (HR = 1.2, 95% CI = 0.7 to 2.2) tumors. CONCLUSIONS: PTEN loss is independently associated with increased risk of lethal progression, particularly in the ERG fusion-negative subgroup. These validated and inexpensive IHC assays may be useful for risk stratification in prostate cancer. |
DOI | 10.1093/jnci/djv346 |
Alternate Journal | J Natl Cancer Inst |
PubMed ID | 26615022 |
PubMed Central ID | PMC4862436 |
Grant List | CA-40360 / CA / NCI NIH HHS / United States CA-34944 / CA / NCI NIH HHS / United States P50 CA090381 / CA / NCI NIH HHS / United States HL-34595 / HL / NHLBI NIH HHS / United States HL-26490 / HL / NHLBI NIH HHS / United States P01 CA087969 / CA / NCI NIH HHS / United States P30 CA006973 / CA / NCI NIH HHS / United States R25 CA112355 / CA / NCI NIH HHS / United States R01CA141298 / CA / NCI NIH HHS / United States R01CA136578 / CA / NCI NIH HHS / United States T32 CA09001 / CA / NCI NIH HHS / United States UM1 CA167552 / CA / NCI NIH HHS / United States CA-097193 / CA / NCI NIH HHS / United States R01 CA040360 / CA / NCI NIH HHS / United States R01 CA136578 / CA / NCI 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.