Loss of microRNA-200a expression correlates with tumor progression in breast cancer

Abstract

MicroRNAs (miRNAs) are 19 similar to 22 nucleotide-long, noncoding, small RNAs, involved in post-transcriptional regulation of many target genes. The miRNA-200 family has been shown to play a crucial role in the epithelial to mesenchymal transition in human cancers. In situ hybridization (ISH) was used to investigate the expression level of miRNA-200a in breast cancers. Formalin-fixed, paraffin embedded (FFPE) tissues from normal breast, ductal carcinoma in situ (DCIS), primary cancers, and metastatic lymph nodes were achieved and constructed to tissue microarrays. MiRNA-200a expression was demonstrated in 95.2% of normal breast tissue samples and 80.4% of DCIS, whereas 178 (58.0%) of 307 breast cancers and 83.3% of metastatic lymph node samples lacked miRNA-200a expression (P < 0.001). Moreover, loss of MiRNA-200a expression correlated with high histologic grade (P = 0.017) and perinodal tumor extension (P = 0.026). However, miRNA-200a expression did not predict tumor recurrence or patient survival. In conclusion, loss of miRNA-200a is frequently observed in breast cancers, especially tumors with high grade histology. These findings suggest that miRNA-200a may play an important role in breast cancer initiation and progression. ISH can be used to detect miRNAs in FFPE sections, and should permit the validation of miRNAs as biomarkers in large clinical samples.