<it>PTEN</it> genomic deletion predicts prostate cancer recurrence and is associated with low AR expression and transcriptional activity

• Main Authors: Choucair Khalil, Ejdelman Joshua, Brimo Fadi, Aprikian Armen, Chevalier Simone, Lapointe Jacques
• Format: Article
• Language: English
• Published: BMC 2012-11-01
• Series: BMC Cancer
• Subjects: Prostate cancer; Prognosis; PTEN; AR
• Online Access: http://www.biomedcentral.com/1471-2407/12/543

<p>Abstract</p> <p>Background</p> <p>Prostate cancer (PCa), a leading cause of cancer death in North American men, displays a broad range of clinical outcome from relatively indolent to lethal metastatic disease. Several genomic alterations have been identified in PCa which may serve as predictors of progression. <it>PTEN</it>, (10q23.3), is a negative regulator of the phosphatidylinositol 3-kinase (PIK3)/AKT survival pathway and a tumor suppressor frequently deleted in PCa. The androgen receptor (AR) signalling pathway is known to play an important role in PCa and its blockade constitutes a commonly used treatment modality. In this study, we assessed the deletion status of <it>PTEN</it> along with AR expression levels in 43 primary PCa specimens with clinical follow-up.</p> <p>Methods</p> <p>Fluorescence <it>In Situ</it> Hybridization (FISH) was done on formalin fixed paraffin embedded (FFPE) PCa samples to examine the deletion status of <it>PTEN</it>. AR expression levels were determined using immunohistochemistry (IHC).</p> <p>Results</p> <p>Using FISH, we found 18 cases of <it>PTEN</it> deletion. Kaplan-Meier analysis showed an association with disease recurrence (<it>P</it>=0.03). Concurrently, IHC staining for AR found significantly lower levels of AR expression within those tumors deleted for <it>PTEN</it> (<it>P</it><0.05). To validate these observations we interrogated a copy number alteration and gene expression profiling dataset of 64 PCa samples, 17 of which were <it>PTEN</it> deleted. We confirmed the predictive value of <it>PTEN</it> deletion in disease recurrence (<it>P</it>=0.03). <it>PTEN</it> deletion was also linked to diminished expression of PTEN (<it>P</it><0.01) and AR (<it>P</it>=0.02). Furthermore, gene set enrichment analysis revealed a diminished expression of genes downstream of AR signalling in <it>PTEN</it> deleted tumors.</p> <p>Conclusions</p> <p>Altogether, our data suggest that <it>PTEN</it> deleted tumors expressing low levels of AR may represent a worse prognostic subset of PCa establishing a challenge for therapeutic management.</p>