NKX3.1, PTEN, ERG and AR Define Genetic Alteration Patterns Correlating with Tumor Progression in Prostate Cancer.
Veit Scheble, Gregor Scharf, Roopika Menon, Pavel Nikolov, Karen Petersen, Falko Fend, Markus Reischl, Sven Perner. University Hospital Tuebingen, Germany; Karlsruhe Institute of Technology, Germany
Background: Prostate Cancer (PCa) is a common and clinically heterogeneous disease. While some PCa cases remain indolent over decades, others progress rapidly. Yet, little is known about genetic alterations resulting in progression of this disease. So far, a large number of genetic aberrations have been identified in PCa, of which the ERG rearrangement, the loss of PTEN and NKX3.1, the gain of CMYC, GOLPH3 and AR are the most common. Unfortunately, none of these genes alone is a strong marker of disease progression. Aim of our study was to assess the alterations of these genes in cases of different stages in order to identify patterns of genetic alterations associated with PCa progression.
Design: We collected consecutive cases of patients who underwent either prostatectomy or metastasis resection. For localized cancer (N0), we identified 138 cases, for regional LN metastasis (N1), we identified 105 patients with primary PCa and corresponding LN metastasis, and for distant metastasis (M1), we identified 39 samples. To assess for alterations of the above mentioned genes, we applied fluorescence in-situ hybridization (FISH) assays.
Results: We found one case with a low level amplification (LLA) of GOLPH 3 in a LN. For CMYC assessment, we found one LLA in a primary focus and the corresponding LN, one LLA in a LN without available primary and two independent LLA and one HLA in M1 cases. PTEN deletions occurred in 3/186 N0 samples, 21/105 N1 cases and 8/39 M1 cases. We found the ERG rearrangement in ∼50% of N0 and N1 samples but only in 10/39 M1 PCa samples. AR amplification could only be detected in M1 cases (14/39). Deletions of NKX3.1 occurred in 55/138 N0, 75/105 N1 and 32/39 M1 samples.
Conclusions: We could show that there are specific genetic alteration patterns that distinguish localized PCa from metastasized PCa. Of note, there are alterations that occur frequently in N1 PCa but at much lesser frequencies in M1. Deletions of PTEN and NKX3.1 in combination with AR amplification characterize the metastatic phenotype. We found the ERG rearrangement in ∼50% of N0 and N1 PCa. Interestingly, we detected an ERG rearrangement frequency of only 25.6% our M1 samples. In concordance with previous reports, AR amplification could only be detected in M1 samples. In summary, the number of alterations increased from localized cancer to progressed PCa.
Category: Genitourinary (including renal tumors)
Monday, February 28, 2011 1:00 PM
Poster Session II # 161, Monday Afternoon