Genomic deletion of PTEN is associated with tumor progression and early PSA recurrence in ERG fusion-positive and fusion-negative prostate cancer

Antje Krohn, Tobias Diedler, Lia Burkhardt, Pascale Sophie Mayer, Colin De Silva, Marie Meyer-Kornblum, Darja Kötschau, Pierre Tennstedt, Joseph Huang, Clarissa Gerhäuser, Malte Mader, Stefan Kurtz, Hüseyin Sirma, Fred Saad, Thomas Steuber, Markus Graefen, Christoph Plass, Guido Sauter, Ronald Simon, Sarah MinnerThorsten Schlomm

研究成果: Article同行評審

273 引文 斯高帕斯(Scopus)

摘要

The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene is often altered in prostate cancer. To determine the prevalence and clinical significance of the different mechanisms of PTEN inactivation, we analyzed PTEN deletions in TMAs containing 4699 hormone-naïve and 57 hormone-refractory prostate cancers using fluorescence in situ hybridization analysis. PTEN mutations and methylation were analyzed in subsets of 149 and 34 tumors, respectively. PTEN deletions were present in 20.2% (458/2266) of prostate cancers, including 8.1% heterozygous and 12.1% homozygous deletions, and were linked to advanced tumor stage (P < 0.0001), high Gleason grade (P < 0.0001), presence of lymph node metastasis (P = 0.0002), hormone-refractory disease (P < 0.0001), presence of ERG gene fusion (P < 0.0001), and nuclear p53 accumulation (P < 0.0001). PTEN deletions were also associated with early prostate-specific antigen recurrence in univariate (P < 0.0001) and multivariate (P = 0.0158) analyses. The prognostic impact of PTEN deletion was seen in both ERG fusion-positive and ERG fusion-negative tumors. PTEN mutations were found in 4 (12.9%) of 31 cancers with heterozygous PTEN deletions but in only 1 (2%) of 59 cancers without PTEN deletion (P = 0.027). Aberrant PTEN promoter methylation was not detected in 34 tumors. The results of this study demonstrate that biallelic PTEN inactivation, by either homozygous deletion or deletion of one allele and mutation of the other, occurs in most PTEN-defective cancers and characterizes a particularly aggressive subset of metastatic and hormone-refractory prostate cancers.

原文English
頁(從 - 到)401-412
頁數12
期刊American Journal of Pathology
181
發行號2
DOIs
出版狀態Published - 2012 8月

All Science Journal Classification (ASJC) codes

  • 病理學與法醫學

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