PTEN Loss as Determined by Clinical-grade Immunohistochemistry Assay Is Associated with Worse Recurrence-free Survival in Prostate Cancer

Tamara Lotan, Wei Wei, Carlos L. Morais, Sarah T. Hawley, Ladan Fazli, Antonio Hurtado-Coll, Dean Troyer, Jesse K. McKenney, Jeffrey Simko, Peter R. Carroll, Martin Gleave, Raymond Lance, Daniel W. Lin, Peter S. Nelson, Ian M. Thompson, Lawrence D. True, Ziding Feng, James D. Brooks

Research output: Contribution to journalArticlepeer-review

Abstract

Background: PTEN is the most commonly deleted tumor suppressor gene in primary prostate cancer (PCa) and its loss is associated with poor clinical outcomes and ERG gene rearrangement. Objective: We tested whether PTEN loss is associated with shorter recurrence-free survival (RFS) in surgically treated PCa patients with known ERG status. Design, setting, and participants: A genetically validated, automated PTEN immunohistochemistry (IHC) protocol was used for 1275 primary prostate tumors from the Canary Foundation retrospective PCa tissue microarray cohort to assess homogeneous (in all tumor tissue sampled) or heterogeneous (in a subset of tumor tissue sampled) PTEN loss. ERG status as determined by a genetically validated IHC assay was available for a subset of 938 tumors. Outcome measurements and statistical analysis: Associations between PTEN and ERG status were assessed using Fisher's exact test. Kaplan-Meier and multivariate weighted Cox proportional models for RFS were constructed. Results and limitations: When compared to intact PTEN, homogeneous (hazard ratio [HR] 1.66, p = 0.001) but not heterogeneous (HR 1.24, p = 0.14) PTEN loss was significantly associated with shorter RFS in multivariate models. Among ERG-positive tumors, homogeneous (HR 3.07, p <0.0001) but not heterogeneous (HR 1.46, p = 0.10) PTEN loss was significantly associated with shorter RFS. Among ERG-negative tumors, PTEN did not reach significance for inclusion in the final multivariate models. The interaction term for PTEN and ERG status with respect to RFS did not reach statistical significance (p = 0.11) for the current sample size. Conclusions: These data suggest that PTEN is a useful prognostic biomarker and that there is no statistically significant interaction between PTEN and ERG status for RFS. Patient summary: We found that loss of the PTEN tumor suppressor gene in prostate tumors as assessed by tissue staining is correlated with shorter time to prostate cancer recurrence after radical prostatectomy. We used highly validated, clinical-grade assays to assess the association of PTEN and ERG protein status with recurrence-free survival (RFS) in a large multi-institutional cohort of surgically treated prostate cancer patients. We show that PTEN protein loss is most strongly associated with shorter RFS if the loss is homogeneous in all tumor tissue sampled. In addition, we demonstrate that there is not a statistically significant interaction between PTEN and ERG with respect to RFS.

Original languageEnglish (US)
Pages (from-to)180-188
Number of pages9
JournalEuropean Urology Focus
Volume2
Issue number2
DOIs
StatePublished - Jun 1 2016

Keywords

  • Biomarker
  • ERG
  • Immunohistochemistry
  • Prostatic carcinoma
  • PTEN
  • Radical prostatectomy

ASJC Scopus subject areas

  • Urology

Fingerprint Dive into the research topics of 'PTEN Loss as Determined by Clinical-grade Immunohistochemistry Assay Is Associated with Worse Recurrence-free Survival in Prostate Cancer'. Together they form a unique fingerprint.

Cite this