PTEN loss detection in prostate cancer: comparison of PTEN immunohistochemistry and PTEN FISH in a large retrospective prostatectomy cohort.

Tamara L Lotan,Guido Sauter,Christina Koop,Sebastian Dwertmann Rico,Ronald Simon,Thorsten Schlomm,Kristen Lecksell,Asmus Heumann,Jessica Hicks

doi:10.18632/oncotarget.19217

Tamara L Lotan, Guido Sauter + Show 7 more

Open Access

https://doi.org/10.18632/oncotarget.19217

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Abstract

PTEN deletion is an established prognostic biomarker in prostate cancer. We compared PTEN immunohistochemistry (IHC) and PTEN fluorescence in situ hybridization (FISH) in the largest existing radical prostatectomy cohort with clinical follow-up data. There was high concordance between IHC and FISH: 93% (3098/3330) of tumors with intact PTEN IHC showed absence of PTEN gene deletion and 66% (720/1087) of cases with PTEN protein loss by IHC showed PTEN gene deletion by FISH. 84% (447/533) of cases with PTEN homozygous gene deletion had PTEN protein loss by IHC. PTEN loss by IHC was associated with reduced PSA recurrence-free survival (RFS) in multivariable models (HR=1.3; 95% CI: 1.16-1.47). Among cases with either PTEN deletion or absence of PTEN deletion by FISH, PTEN loss by IHC was strongly associated with reduced RFS on univariable analysis (p=0.0005 and p<0.0001 respectively). Among cases with intact PTEN by IHC, homozygous (p=0.04) but not heterozygous (p=0.10) PTEN gene deletion was weakly associated with reduced RFS. Among cases with PTEN loss by IHC, both homozygous (p=0.0044) and heterozygous (p=0.0017) PTEN gene deletion were associated with reduced RFS. These data support the utility of PTEN IHC and PTEN FISH as complementary screening tools for PTEN loss in prostate cancer.

Highlights

With increasing numbers of patients deferring definitive therapy for prostate cancer in favor of active surveillance, there is an unmet need for molecular biomarkers that help to distinguish indolent and lethal prostate tumors
These data support the utility of PTEN IHC and PTEN fluorescence in situ hybridization (FISH) as complementary screening tools for PTEN loss in prostate cancer
IHC-based detection of PTEN loss in prostate cancer is less expensive and less time-consuming for the routine screening of prostate tumor specimens, and may be easier to adapt to the current pathology work flow for risk assessment in prostate cancer

Summary

Introduction

With increasing numbers of patients deferring definitive therapy for prostate cancer in favor of active surveillance, there is an unmet need for molecular biomarkers that help to distinguish indolent and lethal prostate tumors. PTEN gene deletion remains one of the few common genomic alterations in prostate cancer that is reproducibly associated with poor outcomes [1,2,3,4,5,6,7,8,9,10,11,12,13]. Because PTEN loss is commonly focal and subclonal in primary prostate tumors [4, 14,15,16], in situ methodologies for PTEN loss detection may be preferable to methods that assess copy number variation based on nucleic acid extraction, such as sequencing. In cases of focal loss, detection of PTEN www.impactjournals.com/oncotarget gene deletion by FISH can be especially challenging and more accomplished by IHC. Only a few studies have directly compared PTEN IHC and PTEN FISH in large cohorts of prostate tumors with clinical outcome information [4, 17, 18, 20,21,22,23,24]

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