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

Abstract

<i>PTEN</i> deletion is an established prognostic biomarker in prostate cancer. We compared PTEN immunohistochemistry (IHC) and <i>PTEN</i> fluorescence <i>in situ</i> 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 <i>PTEN</i> gene deletion and 66% (720/1087) of cases with PTEN protein loss by IHC showed <i>PTEN</i> gene deletion by FISH. 84% (447/533) of cases with <i>PTEN</i> 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 <i>PTEN</i> deletion or absence of <i>PTEN</i> 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) <i>PTEN</i> 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) <i>PTEN</i> gene deletion were associated with reduced RFS. These data support the utility of PTEN IHC and <i>PTEN</i> FISH as complementary screening tools for PTEN loss in prostate cancer.