Aberrant DNA methylation on CpG islands is one of the most consistent epigenetic changes in human cancers, and the process of methylation is catalyzed by the DNA methyltransferases DNMT1, DNMT3a, and DNMT3b. Recent reports demonstrate that deregulation of miR-124a, one of the frequently methylated microRNAs in human cancers, is related to carcinogenesis. The aim of this study was to evaluate the frequencies of methylation of the three genomic loci encoding the miR-124a in primary breast cancers and to investigate their relationships with the clinicopathological characteristics of the tumors and with the expression levels of DNMT1, DNMT3a, and DNMT3b. The methylation status of the three genomic loci encoding the miR-124a (miR-124a-1, miR-124a-2, and miR-124a-3) was analyzed in fresh-frozen tumor samples using methylation-specific PCR in a large series of invasive breast ductal carcinomas (n = 60). Results were correlated to several clinicopathological characteristics of the tumors and to the expression levels of DNMT1, DNMT3a, and DNMT3b, determined by immunohistochemistry. Promoter hypermethylation of miR-124a-1, miR-124a-2, and miR-124a-3 was detected in 53.3, 70, and 36.7% of cases, respectively. Methylation of miR-124a-2 correlated to patients with age higher than 45 years (P = 0.008) and to postmenopausal patients (P = 0.03), whereas methylation of miR-124a-3 correlated significantly to tumor size >20 mm (P = 0.03). Interestingly, simultaneous methylation of the three genes encoding miR-124a correlated significantly with the presence of lymph node metastasis (P = 0.01) and high mitotic score (P = 0.03). No significant correlation was found between promoter hypermethylation of miR-124a and expression of hormone receptors or HER2/neu. With regard to DNMT expression, no correlation was found between DNMT1 or DNMT3a expression and promoter methylation of any tested microRNA. However, DNMT3b overexpression correlates significantly with the hypermethylation of miR-124a-3 (P = 0.03). Our data indicates that miR-124a-1, miR-124a-2, and miR-124a-3 genes are frequently methylated in breast cancer and play a role in tumor growth and aggressivity.
Our results indicate that epigenetic changes frequently occur in both EBV-positive and EBV-negative HL. The rates of these changes were found to vary according to clinico-pathological parameters. These observations probably reflect the multitude of factors involved in HL development and the complexity of their interactions with genetic and/or hormonal factors.
BackgroundPrevious investigations have indicated that CD10 is associated with biological aggressivity in human cancers, but the use of this marker for diagnosis and prognosis is more complex. The aim of this study was to evaluate the expression of CD10 in breast cancer and its association with the clinicopathological features. In addition, we investigated whether a relationship exists between CD10 expression and cancer stem cells.MethodsCD10 expression was examined by the immunohistochemistry in a series of 133 invasive breast carcinoma cases. Results were correlated to several clinicopathological parameters. Cancer stem cell phenotype was assessed by the immunohistochemical analysis of CD44 and ALDH1.ResultsSignificant CD10 expression was found in the fusiform stromal cells in 19.5% of the cases and in the neoplastic cells in 7% of the cases. The stromal CD10 positivity was more frequently found in tumors with lymph node metastasis (p = 0.01) and a high histological grade (p = 0.01). However, CD10 expression by the neoplastic cells correlates with a high histological grade (p = 0.03) and the absence of estrogen (p = 0.002) as well as progesterone (p = 0.001) receptor expression.We also found that CD10 expression by the stromal cells, but not by the neoplastic cells, correlates significantly with the expression of cancer stem cell markers (CD44+/ALDH1+) (p = 0.002).ConclusionThese findings support the role of the stromal CD10 expression in breast cancer progression and dissemination, and suggest a relationship with cancer stem cells.
These findings suggest that CD44 and ALDH1 play a role in the clinical behavior in breast cancer and might be interesting biomarkers and therapeutic targets.
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