ERG alterations and mTOR pathway activation in primary prostate carcinomas developing castration-resistance.
Pathol Res Pract
; 214(10): 1675-1680, 2018 Oct.
Article
em En
| MEDLINE
| ID: mdl-30190183
ABSTRACT
INTRODUCTION:
One of the most common sites of distant metastasization of prostate cancer is bone, but to date reliable biomarkers able to predict the risk and timing of bone metastasization are still lacking. PATIENTS ANDMETHODS:
Surgically resected paraffin embedded samples from 12 primary prostate cancers that developed metachronous bone metastasis at different time points were studied (six cases within 2 years, six cases after 5 years from surgery). A targeted next-generation DNA and RNA sequencing able to assess simultaneously mutations, copy number alterations and fusion events of multiple genes was used. Immunohistochemistry was used to assess mTOR pathway activation.RESULTS:
Rearrangements of ETS family genes, molecular alterations in PTEN and TP53 genes were detected in 10, 6 and 5 cancers, respectively. Nine samples showed TMPRSS2-ERG fusions, which were associated with increased ERG expression at immunohistochemistry. mTOR pathway activation was documented in 6 patients, with a clear trend of prevalence in late-metastatic patients (p = 0.08).CONCLUSIONS:
A simultaneous next-generation targeted DNA and RNA sequencing is applicable on routine formalin-fixed paraffin-embedded tissues to assess the multigene molecular asset of individual prostate cancers. This approach, coupled with immunohistochemistry for ERG and mTOR pathway proteins, may help to better characterize prostate cancer molecular features with a potential impact on clinical decisions.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Adenocarcinoma
/
Biomarcadores Tumorais
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Serina-Treonina Quinases TOR
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Neoplasias de Próstata Resistentes à Castração
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Aged
/
Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article