Immunohistochemical analysis of the endoribonucleases Drosha, Dicer and Ago2 in smooth muscle tumours of soft tissues

Aims: The aims of the present study were to determine the protein levels and cellular distribution of the endoribonucleases Drosha, Dicer and Ago2, major components of the microRNA-processing machinery, in benign and malignant soft tissue smooth muscle tumours, and to correlate the cellular levels of these enzymes with clinicopathological parameters including tumour histopathological grade. Methods and results: Cellular levels of Drosha, Dicer and Ago2 were evaluated in 110 soft tissue leiomyosarcomas (LMS), 31 leiomyomas (LM) and normal smooth muscle (NSM) using immunohistochemistry. Drosha and Dicer were barely detectable in NSM, while augmented levels of these enzymes were observed in LM and LMS. This finding suggests that Drosha and Dicer are implicated in the development of smooth muscle neoplasms. Notably, cellular levels of Dicer were significantly greater in high-grade compared to low-grade LMS, implying its participation in the progression of these neoplasms. Ago2 was detected in NSM, as well as LM and LMS; its cellular levels were not associated with tumour grade. Conclusions: Our results provide novel evidence that Drosha, Dicer and Ago2 are probably involved in the pathobiology of human smooth muscle neoplasms and that Dicer could serve as potentially significant biomarker for LMS progression.