Loss of PTEN Expression Is an Independent Predictor of Recurrence in Prostate Adenocarcinoma
L Schultz, E Platz, J Hicks, A Toubaji, WB Isaacs, A Meeker, AM Demarzo, GJ Netto. Johns Hopkins University, Baltimore
Background: Prostate adenocarcinoma (PCa) shows genetic loss or mutation of at least one PTEN allele in approximately 30–70% of cases. PTEN loss is thought to play an early critical role in prostate oncogenesis possibly in cooperation with ERG oncogene activation. In the current study, we investigated the role of loss of PTEN expression in predicting disease recurrence in a well characterized nested case-control cohort of PCa which we have previously assessed for TMPRSS2-ERG fusion status.
Design: The cohort consisted of 8 TMAs containing paired tumor and normal tissues from radical prostatectomies (RRP) performed at our hospital between 1993 and 2001. They included 209 cases (recurred on follow up) and 209 controls (without PCa recurrence) that were tightly matched for Gleason grade, pTNM stage, ethnicity and patient age. Standard immunohistochemistry for PTEN (Cell Signalling; 1:50 dilution) was performed. PTEN expression was assessed as the percentage of cells staining (extent) and assigned an incremental (0 to 3+) intensity score. Additionally, an "H-score" was calculated in each tumor as the product of intensity x extent.
Results: Mean length of follow-up was 2.6 and 6.2 years in the case and control groups respectively. PTEN expression decreased with patient age (p=0.0002) but did not differ by year of RRP (p=0.8). Overall, PTEN extent of expression was significantly lower in patients with PCa recurrence compared to controls (p=0.02). Furthermore, the control group demonstrated a significantly higher intensity (2+ or 3+) of PTEN staining (p=0.05). Lack of PTEN expression, as well as presence of low PTEN expression (extent <10%), was more frequently encountered in recurrent PCa compared to controls (OR=0.32; p<0.0001). However, the protective effect of PTEN expression was non-linear based on H-score levels.
Conclusions: Lack of PTEN expression in PCa predicted higher likelihood of disease recurrence in our matched case-control cohort. A PTEN immunoexpression extent higher than 10% seems to exert a positive, albeit non-linear, effect on PCa outcome.
Category: Genitourinary (including renal tumors)
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 119, Wednesday Afternoon