Abstract
Objective: The pathogenesis of fibroids is not well understood. Microarray analysis of fibroid tissue identified that some genes are significantly overexpressed, including Delta-like protein (DLK) and Frizzled protein (FZD) (Tsibris, et al. 2002). We postulate that smooth muscle cells of leiomyoma are abnormally differentiated cells derived from uterine stem cells. In addition, the abnormal differentiation leads to the secretion of disordered collagen. Design: Prospective analysis of surgical specimens using immuohistochemistry (IHC), immunoblot and Gomori staining. Materials/Methods: We performed immunohistochemisty using DLK antibody (an imprinted gene involved in cell differentiation), FZD antibody (a key gene in the Wnt cell architecture signaling pathway) and Gomori stain for collagen on paraffin embedded slides of fibroids and myometrium. FZD expression was confirmed by immunoblot. Results: FZD expression was observed in the nucleus of fibroid cells. A halo effect surrounding the stained area was noted. In myometrial cells FZD was seen in the nucleus and cytoplasm. Immunoblotting demonstrated that FZD was upregulated in fibroids compared to myometrium. However, immunohistochemistry showed only nuclear expression of DLK in fibroids, while in myometrium expression was observed in the nucleus and cytoplasm. Gomori staining demonstrated disarrayed collagen with numerous clear spaces and scattered, non-aligned smooth muscle cells in leiomyoma tissue. In contrast, closely packed collagen and aligned smooth muscle fibers were observed in myometrium. Conclusions: These studies suggest that the phenotype of fibroid smooth muscle cells is different from that of the myometrial cells. These altered cells secrete poorly formed collagen, further indicating that fibroids may be a disorder of differentiation. Supported by: NICHD/NIH Intramural Research Training Award Fellowship to Cara Prupas and Chantal Mayers.
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