Sonic Hedgehog signaling pathway in uterine leiomyoma and leiomyosarcoma: Protein and transcriptional expression study and evaluation of the gene methylation profile

Abstract

Leiomyoma and leiomyosarcoma are uterine mesenchymal tumors. These tumors have variable clinical behavior and may lead to death. The leiomyoma is a benign tumor commonly found in women of reproductive age. Leiomyosarcoma represents about 40% of uterine sarcomas. Both are myometrial neoplasms that show the same pattern of cell differentiation, but with completely different clinical progression. Some studies were performed to demonstrate the origin or transformation of leiomyoma to leiomyosarcoma, however, little is known about the mechanisms involved in the development of these tumors and the factors that drive their biological behavior. Recently it was demonstrated that activation of the signaling pathway of Sonic hedgehog (Shh) is related to the development of several types of tumors, since this pathway plays an important role in cell proliferation and differentiation. Mutations or genetic alterations in genes involved in Shh pathway can lead to carcinogenesis. Our aim is to evaluate the expression of genes involved in the Shh signaling pathway, as well as evaluating the presence and degree of gene methylation in samples of leiomyoma and leiomyosarcoma. Thus, 80 samples of leiomyoma, 80 leiomyosarcoma and 20 myometrium samples will be evaluated. The samples will be donated by Department of Gynecology of FMUSP and Department of Pathology of Hospital A. C. Camargo, both in Sao Paulo - Brazil. The paraffin samples will be used in building blocks of tissue microarrays for immunohistochemical evaluation. Genomic DNA and total RNA extracted from fresh samples, will be used in sequencing reactions and quantitative real time PCR. All results will be submitted to statistical analysis. (AU)