INTRODUCTION: MicroRNAs (miRNAs) are a class of small noncoding RNAs that 
control gene expression by targeting mRNAs and triggering either translation 
repression or RNA degradation. Their aberrant expression may be involved in 
human diseases, including cancer. To test the hypothesis that there is a 
specific miRNA expression signature which characterizes male breast cancers, we 
performed miRNA microarray analysis in a series of male breast cancers and 
compared them with cases of male gynecomastia and female breast cancers.
METHODS: Paraffin blocks were obtained at the Department of Pathology of Thomas 
Jefferson University from 28 male patients including 23 breast cancers and five 
cases of male gynecomastia, and from 10 female ductal breast carcinomas. The RNA 
harvested was hybridized to miRNA microarrays (~1,100 miRNA probes, including 
326 human and 249 mouse miRNA genes, spotted in duplicate). To further support 
the microarray data, an immunohistochemical analysis for two specific miRNA gene 
targets (HOXD10 and VEGF) was performed in a small series of male breast 
carcinoma and gynecomastia samples.
RESULTS: We identified a male breast cancer miRNA signature composed of a large 
portion of underexpressed miRNAs. In particular, 17 miRNAs with increased 
expression and 26 miRNAs with decreased expression were identified in male 
breast cancer compared with gynecomastia. Among these miRNAs, some had 
well-characterized cancer development association and some showed a deregulation 
in cancer specimens similar to the one previously observed in the published 
signatures of female breast cancer. Comparing male with female breast cancer 
miRNA expression signatures, 17 significantly deregulated miRNAs were observed 
(four overexpressed and 13 underexpressed in male breast cancers). The HOXD10 
and VEGF gene immunohistochemical expression significantly follows the 
corresponding miRNA deregulation.
CONCLUSIONS: Our results suggest that specific miRNAs may be directly involved 
in male breast cancer development and that they may represent a novel diagnostic 
tool in the characterization of specific cancer gene targets.