RESUMO
The diagnosis of prostatic cancer present in a limited amount within needle biopsy tissue, is often challenging. The most common mimickers giving rise to false-positive cancer diagnosis are atypical adenomatous hyperplasia, prostatic intraepithelial neoplasia, atrophy and post-atrophic hyperplasia. Various diagnostic criteria including assessment of basal cells should be used for diagnosis of limited carcinoma. Immunohistochemical staining for both basal cells, such as 34betaE12 and p63, and AMACR, which label the cytoplasm of approximately 80% of prostatic adenocarcinoma, may be a useful adjunct in the diagnosis of limited prostatic cancer. However there are problems with both sensitivity and specificity. When the glands lacking sufficient criteria to establish a definitive carcinoma is present, we use the term 'atypical small acinar proliferation'.
Assuntos
Neoplasias da Próstata/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Biópsia por Agulha , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Masculino , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/patologia , Neoplasia Prostática Intraepitelial/diagnóstico , Neoplasia Prostática Intraepitelial/patologia , Neoplasias da Próstata/diagnósticoRESUMO
The methylation status of 7 genes was examined in four cell lines, 36 samples of benign prostatic hyperplasia (BPH), 20 samples of prostatic intraepithelial neoplasia (PIN) and 109 samples of prostate cancer (PCa), using methylation-specific PCR (MSP): the pi-class glutathione S-transferase (GSTP1), retinoic acid receptor beta 2(RARbeta2), androgen receptor (AR), death-associated protein kinase (DAPK), tissue inhibitor of metalloproteinase-3 (TIMP-3), O(6)-methylguanine DNA methyltransferase (MGMT), and hypermethylated in cancer-1 (HIC-1). The frequencies of methylation in PCa were 88% for GSTP1, 78% for RARbeta2, 36% for DAPK, 15% for AR, 6% for TIMP-3, and 2% for MGMT, whereas the values were 11% for AR and DAPK, 6% for TIMP-3, 3% for GSTP1, and 0 for RARbeta2 and MGMT in BPH. Aberrant methylation of the GSTP1 and RARbeta2 genes was detected in 30% and 20% of PIN, respectively. Most samples of BPH and PCa were positive for HIC-1 methylation. Regarding accumulation of methylated cancer-related genes, there were significant correlations between PCa and BPH as well as PIN and BPH. In the present study, a high frequency of aberrant promoter methylation of the GSTP1 and RARbeta2 genes was noted in PCa. Our findings suggest that methylation of cancer-related genes may be involved in carcinogenesis of the prostate.
Assuntos
Biomarcadores Tumorais/genética , Metilação de DNA , Proteínas de Neoplasias/genética , Regiões Promotoras Genéticas/genética , Neoplasias da Próstata/genética , Idoso , Idoso de 80 Anos ou mais , Proteínas Reguladoras de Apoptose , Proteínas Quinases Dependentes de Cálcio-Calmodulina/genética , Primers do DNA/química , Proteínas Quinases Associadas com Morte Celular , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Glutationa S-Transferase pi , Glutationa Transferase/genética , Humanos , Isoenzimas/genética , Masculino , Pessoa de Meia-Idade , O(6)-Metilguanina-DNA Metiltransferase/genética , Reação em Cadeia da Polimerase , Antígeno Prostático Específico/genética , Hiperplasia Prostática/enzimologia , Hiperplasia Prostática/genética , Hiperplasia Prostática/patologia , Neoplasia Prostática Intraepitelial/enzimologia , Neoplasia Prostática Intraepitelial/genética , Neoplasia Prostática Intraepitelial/patologia , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/patologia , Receptores Androgênicos/genética , Receptores do Ácido Retinoico/genética , Inibidor Tecidual de Metaloproteinase-3/genéticaRESUMO
Transcriptional silencing of cancer-related genes by DNA methylation is observed in various cancers. To identify genes controlled by methylation in prostate cancer, we used cDNA microarray analysis to investigate gene expression in prostate cancer cell lines LNCaP and DU145 treated with a methyltransferase inhibitor alone or together with a histone deacetylase inhibitor. We detected significant changes (3.4-5.7%) in gene expression in prostate cancer cell lines with the drug treatments. Among the affected genes, that for the vascular endothelial growth factor receptor 1 (VEGFR-1) was re-expressed in LNCaP and DU145 after the drug treatments. Bisulfite sequencing revealed the promoter and exon 1 of the VEGFR-1 to be hypermethylated in the cell lines. These results support the idea that methylation is associated with loss of VEGFR-1 mRNA expression in prostate cancer cell lines. Combined bisulfite restriction analysis (COBRA) showed the gene to be methylated in 24 (38.1%) of 63 primary local prostate cancer samples, while in all 13 benign prostate samples it was not. These findings indicate that methylation of VEGFR-1 is related with prostatic carcinogenesis.