Overexpression of SPARC protein contrasts with its transcriptional silencing by aberrant hypermethylation of SPARC CpG-rich region in endometrial carcinoma

Secreted protein acidic and rich in cysteine (SPARC) is a secreted matricellular glycoprotein involved in crucial processes that occur during cancer. This study explored the occurrence of deregulated expression of SPARC in endometrial carcinomas, since it has been associated with the progression of other tumor types. We analyzed the expression of SPARC in endometrial carcinomas by TaqMan, Western blotting and immunohistochemistry. The CpG island methylation status of SPARC was evaluated by bisulfite sequencing method. A significant down-regulation of SPARC mRNA expression (p<0.001) was observed in endometrial tumor tissues, regardless of their microsatellite instability status (MSI). The down-regulation can be accounted for by aberrant hypermethylation of its CpG-rich region, since we demonstrate that SPARC is a frequent target of this epigenetic event in this pathology. Although, differential expression of SPARC is already known in other cancer types, we report that down-regulation of the SPARC gene in endometrial tumors, formed by at least 80% of epithelial tumor cells, contrasts with a frequent overexpression of SPARC protein, with strong immunoreactivity in stromal cells. These results indicate a cell type specific expression of SPARC in endometrial carcinomas. Accumulation of SPARC protein in most tumors compared to normal tissues (p<0.025), suggests an important role in the carcinogenesis of endometrial tumors. SPARC overexpression can be a useful molecular tool that may contribute to the diagnosis of this disease.