The 17-Gene Genomic Prostate Score Assay Predicts Outcome After Radical Prostatectomy Independent of PTEN Status

• Published in: Urology (Ridgewood, N.J.) Vol. 121; pp. 132 - 138
• Main Authors: Magi-Galluzzi, Cristina, Isharwal, Sudhir, Falzarano, Sara M., Tsiatis, Athanasios, Dee, Anne, Maddala, Tara, Knezevic, Dejan, Febbo, Phillip G., Lawrence, Jeffrey, Klein, Eric A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2018
• Subjects: Aged; Biomarkers, Tumor - analysis; Gene Expression Profiling - methods; Genomics - methods; Humans; Lymphatic Metastasis - diagnosis; Male; Middle Aged; Neoplasm Grading; Neoplasm Recurrence, Local - diagnosis; Neoplasm Staging; Prognosis; Prostate-Specific Antigen - analysis; Prostatectomy - adverse effects; Prostatectomy - methods; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Prostatic Neoplasms - surgery; PTEN Phosphohydrolase - analysis; Research Design; Risk Assessment - methods; Salvage Therapy - methods
• ISSN: 0090-4295; 1527-9995
• DOI: 10.1016/j.urology.2018.07.018

To compare the ability of loss of phosphatase and tensin homolog (PTEN) and Genomic prostate score assay (GPS) in predicting the biochemical-recurrence (BCR) and clinical-recurrence (CR) after radical prostatectomy (RP) for clinically localized prostate cancer (PCa). Three hundred seventy seven patients with and without CR were retrospectively selected by stratified cohort sampling design from RP database. PTEN status (by immunohistochemistry [IHC] and fluorescence in situ hybridization [FISH]) and GPS results were determined for RP specimens. BCR was defined as Prostate Specific Antigen (PSA) ≥ 0.2 ng/mL or initiation of salvage therapy for a rising PSA. CR was defined as local recurrence and/or distant metastases. Baseline mean age, PSA, and GPS score for the cohort were 61.1 years, 8 ng/dL, and 32.8. PTEN loss was noted in 38% patients by FISH and 25% by IHC. The concordance between FISH and IHC for PTEN loss was 66% (Kappa coefficient 0.278; P < .001). On univariable analysis, loss of PTEN by FISH or IHC was associated with BCR and CR (P < .05). However, after adjusting for GPS results, PTEN loss was not a significant predictor for CR or BCR (P > .1). The GPS result remained strongly associated with CR and BCR after adjusting for PTEN status (P < .001). PTEN status and GPS results only weakly correlated. GPS was widely distributed regardless of PTEN status indicating the biological heterogeneity of PCa even in PTEN-deficient cases. GPS is a significant predictor of aggressive PCa, independent of PTEN status. After adjustment for GPS results, PTEN was not independently associated with recurrence for PCa.