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Fluorescence in situ hybridization study shows association of PTEN deletion with ERG rearrangement during prostate cancer progression.

ABSTRACT: The link between ERG rearrangement and PTEN (phosphatase and tensin homolog deleted on chromosome 10) deletion is unclear in prostate cancer progression. Using fluorescence in situ hybridization, we systematically validated the frequency and distribution of ERG and PTEN aberrations in a cohort of 73 benign prostate tissues, 59 high-grade prostatic intraepithelial neoplasia (HGPIN) foci, 281 localized prostate cancer and 47 androgen-independent metastatic prostate cancer patients. Overall, ERG rearrangement was present in 15% (5/33) of HGPIN, 45% (121/267) of localized cancers and 35% (15/43) of metastases. By contrast, PTEN deletion was identified in 9% (3/33) of HGPIN, 17% (42/251) of localized cancers and 54% (22/41) of metastases, of which 0%, 40% (17/42) and 45% (10/22) were homozygous, respectively. Concomitance of ERG rearrangement and PTEN deletion was observed in a subset of HGPIN. Significantly, association between PTEN deletion and ERG rearrangement was present both in localized cancers (P=0.0008) and metastases (P=0.02). Further, immunohistochemistry revealed significant correlation of decreased PTEN protein expression with PTEN genomic deletion both in localized and metastatic cancer. Of note, ERG aberration, but not PTEN deletion, was consistently identical both in localized cancer and adjacent HGPIN. Similarly, whereas all metastases (41/41, 100%) shared the same ERG status across multiple sites from the same patient, 5% (2/41) of cases showed discordance for PTEN deletion status across multiple sites. Collectively, our data support PTEN deletion as a late genetic event in human prostate cancer, presumably a 'second hit' after ERG rearrangement. PTEN deletion and ERG rearrangement may cooperate, but contribute at different stages, in prostate cancer progression.

SUBMITTER: Han B

PROVIDER: S-EPMC2760294 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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Fluorescence in situ hybridization study shows association of PTEN deletion with ERG rearrangement during prostate cancer progression.

Han Bo B Mehra Rohit R Lonigro Robert J RJ Wang Lei L Suleman Khalid K Menon Anjana A Palanisamy Nallasivam N Tomlins Scott A SA Chinnaiyan Arul M AM Shah Rajal B RB

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 20090501 8

The link between ERG rearrangement and PTEN (phosphatase and tensin homolog deleted on chromosome 10) deletion is unclear in prostate cancer progression. Using fluorescence in situ hybridization, we systematically validated the frequency and distribution of ERG and PTEN aberrations in a cohort of 73 benign prostate tissues, 59 high-grade prostatic intraepithelial neoplasia (HGPIN) foci, 281 localized prostate cancer and 47 androgen-independent metastatic prostate cancer patients. Overall, ERG re ...[more]

PMID: 19407851

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Project description:BackgroundProstate Cancer (PCa) is the second most prevalent cancer among U.S. males. In recent decades many men with low risk PCa have been over diagnosed and over treated. Given significant co-morbidities associated with definitive treatments, maximizing patient quality of life while recognizing early signs of aggressive disease is essential. There remains a need to better stratify newly diagnosed men according to the risk of disease progression, identifying, with high sensitivity and specificity, candidates for active surveillance versus intervention therapy. The objective of this study was to select fluorescence in situ hybridization (FISH) panels that differentiate non-progressive from progressive disease in patients with low and intermediate risk PCa.MethodsWe performed a retrospective case-control study to evaluate FISH biomarkers on specimens from PCa patients with clinically localised disease (T1c-T2c) enrolled in Watchful waiting (WW)/Active Surveillance (AS). The patients were classified into cases (progressed to clinical intervention within 10 years), and controls (did not progress in 10 years). Receiver Operating Characteristic (ROC) curve analysis was performed to identify the best 3-5 probe combinations. FISH parameters were then combined with the clinical parameters ─ National Comprehensive Cancer Network (NNCN) risk categories ─ in the logistic regression model.ResultsSeven combinations of FISH parameters with the highest sensitivity and specificity for discriminating cases from controls were selected based on the ROC curve analysis. In the logistic regression model, these combinations contributed significantly to the prediction of PCa outcome. The combination of NCCN risk categories and FISH was additive to the clinical parameters or FISH alone in the final model, with odds ratios of 5.1 to 7.0 for the likelihood of the FISH-positive patients in the intended population to develop disease progression, as compared to the FISH-negative group.ConclusionsCombinations of FISH parameters discriminating progressive from non-progressive PCa were selected based on ROC curve analysis. The combination of clinical parameters and FISH outperformed clinical parameters alone, and was complimentary to clinical parameters in the final model, demonstrating potential utility of multi-colour FISH panels as an auxiliary tool for PCa risk stratification. Further studies with larger cohorts are planned to confirm these findings.

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Fluorescence in situ hybridization study shows association of PTEN deletion with ERG rearrangement during prostate cancer progression.

Publications

Fluorescence in situ hybridization study shows association of PTEN deletion with ERG rearrangement during prostate cancer progression.

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