Oncotarget

Research Papers:

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

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

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Oncotarget. 2017; 8:65566-65576. https://doi.org/10.18632/oncotarget.19217

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Abstract

Tamara L. Lotan1,2, Asmus Heumann3, Sebastian Dwertmann Rico3, Jessica Hicks1, Kristen Lecksell1, Christina Koop3, Guido Sauter3, Thorsten Schlomm4,5 and Ronald Simon3

1Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA

2Oncology, Johns Hopkins School of Medicine, Baltimore, MD, USA

3Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

4Martini-Klinik Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Correspondence to:

Tamara L. Lotan, email: tlotan1@jhmi.edu

Keywords: prostatic carcinoma, PTEN, fluorescence in situ hybridization, immunohistochemistry, biomarker

Received: April 04, 2017     Accepted: April 27, 2017     Published: July 10, 2017

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.


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