Abstract 320: Association of higher Gleason grade with presence of PTEN deletion in prostatic adenocarcinoma

Abstract

Abstract Prostatic adenocarcinoma (CaP) is one of the most histologically heterogeneous of epithelial malignancies. The Gleason score is widely accepted as the standard for histologic grading and determining prognosis of prostate malignancies. The tumor often presents with a multifocal distribution though the gland and different Gleason grades may be present in different foci. The current study was undertaken to compare the association of genomic alterations with the Gleason grades of individual adenocarcinoma foci. Genomic deletion of the PTEN gene in routine formalin-fixed paraffin-embedded (FFPE) pathology sections can be readily assayed by fluorescence in situ hybridization (FISH). Data from our group and others has shown that the genomic deletion of the PTEN tumor suppressor gene and the disruption of the ETS gene family, play a central role in prostate cancer and are likely to be associated with Gleason grade. In this study CaP samples were thoroughly analyzed to identify PTEN heterogeneity, within or between foci in multifocal tumors. This study was designed to retrospectively assess the overall frequency with which PTEN deletions and TMPRSS2-ERG fusion rearrangements occur individually and simultaneously, and their clinical impact through FISH analysis using well-annotated high-throughput tissue microarrays (TMAs) derived from 128 patients with CaP. In addition, four-color FISH analysis of the PTEN deletion was used to precisely detect the interstitial deletion of genomic content from this region of chromosome 10q and evaluate the tumor heterogeneity. Genomic PTEN deletion was observed in 55 of 128 (43%) patients with CaP (hemizygous = 41 and homozygous = 14 CaP). TMPRSS2-ERG fusion was observed in 58 of 129 (45%). We specifically examined the relationship between PTEN deletion and TMPRSS2-ERG fusion status, Gleason pattern and clinical behavior of CaP. Importantly, PTEN deletions were significantly associated with a higher primary Gleason pattern grade 4 (p=0.000), lymphovascular invasion (p=0.051), and higher percentage of prostate involved by tumor (p=0.0064). Although TMPRSS2-ERG fusions showed a strong relationship with PTEN deletions (p=0.007), TMPRSS2-ERG fusions did not show any clinical correlation. In conclusion, our findings indicated that PTEN deletion FISH can be applied to CaP samples to accurately stratify patients into risk categories and to guide decision-making with respect to the optimal management of CaP patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 320. doi:10.1158/1538-7445.AM2011-320