Aims: Known as modulators of receptor tyrosine kinase signalling, Sprouty proteins are implicated in regulation of cellular processes central to cancer development, progression and dissemination. Although deregulation of this protein family has been investigated in a variety of human cancers, little is known about their status in epithelial ovarian cancer (EOC). We previously reported inverse correlation of the Spry1 expression with ovarian cancer cell proliferation, migration, invasion and survival. In the present study, the expression status of Spry1 protein in patients with EOC was retrospectively evaluated and its clinical relevance and prognostic significance was explored.
Methods: Matched tumour and normal tissue samples from 100 patients with EOC were immunohistochemically stained and scored for the expression of Spry1 protein. Expression of ERK, p-ERK and Ki67 and their correlation with Spry1 expression were also evaluated. In addition, correlation between Spry1 levels and clinicopathological characteristics was analysed and, finally, predictive significance of Spry1 for overall survival (OS) and disease-free survival (DFS) were assessed.
Results: Spry1 was found to be significantly downregulated in tumour tissues (p=0.004). Spry1 showed significant inverse correlation with p-ERK/ERK (p=0.045), Ki67 (p=0.010), disease stage (p=0.029), tumour grade (p=0.037), recurrence (p=0.001) and lymphovascular invasion (p=0.042). It was revealed that Spry1 low-expressing patients had significantly poorer OS (p=0.010) and DFS (p=0.012) than those with high expression of Spry1. Multivariate analysis showed that high Spry1 (p=0.030), low stage (p=0.048) and no residual tumour (p=0.007) were independent prognostic factors for a better OS, among which high Spry1 (p=0.035) and low stage (p=0.035) remained as independent predictors of DFS, too.
Conclusions: We report for the first time downregulation of Spry1 protein in epithelial ovarian cancer with significant impact on tumour behavior and prognostic value as independent predictors of survival and recurrence.