Association of Smoothelin, a Cytoskeletal Component of Smooth Muscle Cells, With the Proliferative Features of Uterine Smooth Muscle Tumors

Smoothelin, a cytoskeletal protein expressed in smooth muscle cells (SMCs), colocalizes with α-smooth muscle actin and is typically restricted to the cytoplasm. Interestingly, in malignant smooth muscle tumors (SMTs), particularly uterine leiomyosarcoma (LMS), aberrant nuclear localization of smoothelin has been observed, though the underlying mechanism remains unclear. To investigate, 99 uterine SMT cases were analyzed, comprising 26 LMS and 73 non-LMS (typical leiomyoma, cellular leiomyoma, mitotically active leiomyoma, and tumors of uncertain malignant potential). Histopathological and immunohistochemical evaluations included mitotic activity, Ki-67 index, and smoothelin expression. In vitro, two humans uterine LMS cell lines (SK-LMS-1, SK-UT-1) and a primary uterine SMC line under proliferative conditions were examined. Nuclear smoothelin expression was significantly more frequent in LMS compared with non-LMS. Within LMS tissues, both cytoplasmic and nuclear positivity were noted. Smoothelin-positive regions exhibited significantly higher mitotic activity, whereas Ki-67 labeling and nuclear size variation showed no association with localization. In cultured LMS cells, proliferation correlated with increased nuclear smoothelin positivity. These findings suggest that smoothelin is linked to proliferative capacity in SMTs, and its altered subcellular distribution may have potential utility in the pathological evaluation of SMTs.