Histologically benign PI-RADS 4 and 5 lesions contain cancer-associated epigenetic alterations.
Prostate
; 82(1): 145-153, 2022 01.
Article
em En
| MEDLINE
| ID: mdl-34672371
ABSTRACT
BACKGROUND:
The detection rate of clinically significant prostate cancer has improved with the use of multiparametric magnetic resonance imaging (mpMRI). Yet, even with MRI-guided biopsy 15%-35% of high-risk lesions (Prostate Imaging-Reporting and Data System [PI-RADS] 4 and 5) are histologically benign. It is unclear if these false positives are due to diagnostic/sampling errors or pathophysiological alterations. To better understand this, we tested histologically benign PI-RAD 4 and 5 lesions for common malignant epigenetic alterations. MATERIALS ANDMETHODS:
MRI-guided in-bore biopsy samples were collected from 45 patients with PI-RADS 4 (n = 31) or 5 (n = 14) lesions. Patients had a median clinical follow-up of 3.8 years. High-risk mpMRI patients were grouped based on their histology into biopsy positive for tumor (BPT; n = 28) or biopsy negative for tumor (BNT; n = 17). From these biopsy samples, DNA methylation of well-known tumor suppressor genes (APC, GSTP1, and RARß2) was quantified.RESULTS:
Similar to previous work we observed high rates of promoter methylation at GSTP1 (92.7%), RARß2 (57.3%), and APC (37.8%) in malignant BPT samples but no methylation in benign TURP chips. Interestingly, similar to the malignant samples the BNT biopsies also had increased methylation at the promoter of GSTP1 (78.8%) and RARß2 (34.6%). However, despite these epigenetic alterations none of these BNT patients developed prostate cancer, and those who underwent repeat mpMRI (n = 8) demonstrated either radiological regression or stability.CONCLUSIONS:
Histologically benign PI-RADS 4 and 5 lesions harbor prostate cancer-associated epigenetic alterations.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
1_ASSA2030
/
2_ODS3
Base de dados:
MEDLINE
Assunto principal:
Próstata
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Neoplasias da Próstata
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Ultrassonografia de Intervenção
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Metilação de DNA
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Biópsia Guiada por Imagem
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Imageamento por Ressonância Magnética Multiparamétrica
Tipo de estudo:
Diagnostic_studies
/
Risk_factors_studies
Limite:
Humans
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Male
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Middle aged
Idioma:
En
Revista:
Prostate
Ano de publicação:
2022
Tipo de documento:
Article