Role of SIX1, EYA2, and E-cadherin in ovarian carcinoma. Evidence on epithelial-mesenchymal transition from an immunohistochemical study

This study aims to investigate the expression of SIX1, EYA2, and E-cadherin in ovarian cancer (OC). It was conducted on 97 cases of surface epithelial tumors (SEOTs). Immunohistochemistry (IHC) staining for the three markers was applied to archival paraffin-embedded sections. Results of semi-quantitative scoring were statistically compared, correlated with clinic-pathologic parameters, response to therapy and with patient survival. Results: There was a significant association of SIX1 expression in the intratumoral stroma (ITS) with malignant cases (P < 0.0001). There was a significant direct correlation between tumour cell expression of SIX1 and EYA2 (P = 0.03) and an inverse correlation between SIX1 and E-cadherin (P = 0.03). Additionally, there were direct correlations between SIX1 expression and larger tumour size (P = 0.05), high mitosis (P < 0.0001), and advanced FIGO stage (P = 0.06), and between EYA2 expression and LN metastasis (P = 0.02), and low apoptotic index (P = 0.007). Only SIX1 expression in ITS affected the patient survival by univariate analysis (P = 0.004). Conclusions: SIX1/EYA2 complex may have a poor prognostic role in OC. SIX1 expression in ITS may be used as a predictive marker of stromal invasion in ovarian borderline tumors and could affect patients' survival in OC. SIX1, EYA2, and E-cadherin may constitute a pathway that could be targeted to stop the progression of SEOTs.