PTEN Loss as Determined by Clinical-grade Immunohistochemistry Assay Is Associated with Worse Recurrence-free Survival in Prostate Cancer.
BACKGROUND
PTENis the most commonly deleted tumor suppressor gene in primary prostate cancer (PCa) and its loss is associated with poor clinical outcomes andERGgene rearrangement.


OBJECTIVE
We tested whether PTEN loss is associated with shorter recurrence-free survival (RFS) in surgically treated PCa patients with known ERG status.


METHODS
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.


METHODS
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.


CONCLUSIONS
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.


RESULTS
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.
Pathology Department, Johns Hopkins School of Medicine, Baltimore, MD, USA; Oncology Department, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Tamara L
TL
Lotan
MD Anderson Cancer Center, Houston, TX, USA.
Wei
W
Wei
Pathology Department, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Carlos L
CL
Morais
Canary Foundation, Palo Alto, CA, USA.
Sarah T
ST
Hawley
Vancouver Prostate Centre, Vancouver, BC, Canada.
Ladan
L
Fazli
Vancouver Prostate Centre, Vancouver, BC, Canada.
Antonio
A
Hurtado-Coll
Pathology Department, Eastern Virginia Medical School, Norfolk, VA, USA; Urology Department, Eastern Virginia Medical School, Norfolk, VA, USA.
Dean
D
Troyer
Pathology Department, Cleveland Clinic, Cleveland, OH, USA.
Jesse K
JK
McKenney
Pathology Department, University of California-San Francisco, San Francisco, CA, USA; Urology Department, University of California-San Francisco, San Francisco, CA, USA.
Jeffrey
J
Simko
Urology Department, University of California-San Francisco, San Francisco, CA, USA.
Peter R
PR
Carroll
Vancouver Prostate Centre, Vancouver, BC, Canada.
Martin
M
Gleave
Urology Department, Eastern Virginia Medical School, Norfolk, VA, USA.
Raymond
R
Lance
Urology Department, University of Washington, Seattle, WA, USA.
Daniel W
DW
Lin
Oncology Department, University of Washington, Seattle, WA, USA; Pathology Department, University of Washington, Seattle, WA, USA.
Peter S
PS
Nelson
Urology Department, University of Texas Health Science Center, San Antonio, TX, USA.
Ian M
IM
Thompson
Pathology Department, University of California-San Francisco, San Francisco, CA, USA.
Lawrence D
LD
True
MD Anderson Cancer Center, Houston, TX, USA.
Ziding
Z
Feng
Urology Department, Stanford University School of Medicine, Stanford, CA, USA.
James D
JD
Brooks
Biomarker; ERG; Immunohistochemistry; PTEN; Prostatic carcinoma; Radical prostatectomy