Clinical significance of secreted protein acidic and rich in cystein in esophageal carcinoma and its relation to carcinoma progression

Abstract

Background: Secreted protein acidic and rich in cystein (SPARC) is a small extramatrix-associated protein. Its production increases during angiogenesis and enhances matrix metalloproteinase-2 (MMP-2) expression. The goal of this study was to show the clinical relevance of SPARC and its relation to MMP-2 expression in esophageal carcinoma patients.

Methods: The authors investigated SPARC mRNA expression in 48 tissue samples of esophageal tumors characterized by MMP-2 mRNA expression in a Northern blot analysis. Western blot analysis and immunohistochemistry were also performed in esophageal carcinoma tissue samples.

Results: All 48 tissue specimens had high expression of SPARC mRNA. Quantitative evaluation showed that high SPARC mRNA was associated significantly with lymph node metastasis (P = 0.05) and poorer prognosis (P = 0.025). Expression of SPARC mRNA was associated significantly with MMP-2 mRNA expression (R = 0.65; P < 0.01). Both SPARC and MMP-2 were immunolocalized intensely in carcinoma and stromal cells, whereas normal esophageal mucosa and submucosa did not express SPARC. The 35-kilodalton cleaved SPARC was detected in esophageal carcinoma tissue specimens by Western blot analysis and it was associated with MMP-2 mRNA expression.

Conclusions: In terms of clinical significance, SPARC accumulation may reflect a functional correlation with MMP-2 and the associated expression could play a key role in the progression of esophageal carcinoma.