A Prospective Investigation of PTEN Loss and ERG Expression in Lethal Prostate Cancer

被引：143

作者：

Ahearn, Thomas U. ^{[1
,14
]}

Pettersson, Andreas ^{[1
,3
]}

Ebot, Ericka M. ^{[1
]}

Gerke, Travis ^{[1
]}

Graff, Rebecca E. ^{[1
,4
]}

Morais, Carlos L. ^{[5
]}

Hicks, Jessica L. ^{[5
]}

Wilson, Kathryn M. ^{[1
,6
,7
]}

Rider, Jennifer R. ^{[1
,6
,7
]}

Sesso, Howard D. ^{[1
,8
,9
]}

Fiorentino, Michelangelo ^{[10
]}

Flavin, Richard ^{[11
]}

Finn, Stephen ^{[11
]}

Giovannucci, Edward L. ^{[1
,2
,6
,7
]}

Loda, Massimo ^{[12
]}

Stampfer, Meir J. ^{[1
,2
,6
,7
]}

De Marzo, Angelo M. ^{[5
,13
,14
]}

Mucci, Lorelei A. ^{[1
,6
,7
]}

Lotan, Tamara L. ^{[5
,13
]}

机构：

[1] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[2] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA

[3] Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden

[4] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA

[5] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA

[6] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA

[7] Harvard Univ, Sch Med, Boston, MA 02115 USA

[8] Brigham & Womens Hosp, Dept Med, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA

[9] Brigham & Womens Hosp, Dept Med, Div Aging, 75 Francis St, Boston, MA 02115 USA

[10] St Orsola Marcello Malpighi Hosp, Addarii Inst, Pathol Unit, Bologna, Italy

[11] Trinity Coll Dublin, Dept Histopathol Res, Dublin, Ireland

[12] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[13] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA

[14] Johns Hopkins Univ, Sch Med, Dept Urol, Baltimore, MD 21205 USA

来源：

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE | 2016年 / 108卷 / 02期

基金：

瑞典研究理事会;

关键词：

GENOMIC DELETION; BIOCHEMICAL RECURRENCE; AFRICAN-AMERICAN; GENE FUSIONS; PROTEIN LOSS; HIGH-RISK; PROGRESSION; HETEROGENEITY; REARRANGEMENT; FREQUENCY;

D O I：

10.1093/jnci/djv346

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 clinicalpathologic 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.

引用

页数：9

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