RESUMO
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.
Assuntos
Proteínas Argonautas/metabolismo , RNA Helicases DEAD-box/metabolismo , Ribonuclease III/metabolismo , Tumor de Músculo Liso/patologia , Neoplasias de Tecidos Moles/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Endorribonucleases/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Leiomioma/metabolismo , Leiomioma/patologia , Leiomiossarcoma/metabolismo , Leiomiossarcoma/patologia , Masculino , Pessoa de Meia-Idade , Tumor de Músculo Liso/metabolismo , Neoplasias de Tecidos Moles/metabolismoRESUMO
In the present study we assessed the expression and distribution of endoribonuclease Dicer in soft tissue tumors and correlated its cellular levels with clinicopathological parameters, including clinical outcome. Dicer was expressed in the tested cell line as well as in the majority of the sarcomas examined. Staining intensity was significantly higher in sarcomas compared with benign neoplasms and in high-grade compared with low-grade tumors. Elevated Dicer immunoreactivity was strongly associated with poor outcome and Dicer cellular levels were an independent negative prognostic factor.