engleski

Expression of Dishevelled family proteins DVL1, DVL2 and DVL3 in serous ovarian carcinomas

Wnt is an evolutionarily conserved signaling pathway, which plays a key role in regulating many biological processes, such as differentiation, adhesion, cell proliferation, cell survival, and apoptosis. These processes are crucial for tissue regeneration, maintenance regulation and differentiation of stem cells in the adult organism. Binding of the Wnt ligands along with Frizzled receptor activates Dishevelled (DVL) proteins, resulting in increased activity of β- catenin that binds to TCF/LEF transcription factor and thus activates targeted genes. Aberrant activation of Wnt signaling pathway through increased expression of DVL proteins, key negative regulators of β-catenin degradation, is associated with tumor development. In the present study, we explored DVL1, DVL2 and DVL3 protein expression in a cohort of serous ovarian carcinomas. Formalin- fixed paraffin-embedded samples of 11 low-grade serous ovarian carcinomas (LGSC), 37 high-grade serous ovarian carcinomas (HGSC) and seven normal ovarian tissues were used for this study. DVL1, DVL2 and DVL3 protein expression were semi- quantitatively analyzed using immunohistochemistry. Kaplan–Meier survival plots were constructed to estimate the overall survival by DVL1, DVL2 and DVL3 protein expression and FIGO stage. Expression of DVL2 and DVL3 were significantly higher in both LGSC (p=0.002 and p=0.002, respectively) and HGSC (p=0.001 and p=0.001, respectively) compared with normal ovarian tissues. DVL1 protein expression was significantly higher in LGSC compared with HGSC (p=0.02) and normal ovarian tissues (p=0.011). In HGSC, DVL2 and DVL3 protein expression was significantly higher than DVL1 protein expression (p<0.001 and p<0.001, respectively). The Spearman correlation test showed that there was a significant positive correlation between DVL2 and DVL3 expression in LGSC (r=0.743, p=0.009). There was no statistically significant difference in expression of DVL2 and DVL3 proteins between LGSC and HGSC, and DVL1 protein in HGSC in comparison with normal ovarian tissues. Survival analysis revealed that poor survival was associated with advanced FIGO stage in HGSC and LGSC (p=0.047 ; p=0.026). Our preliminary results did not show statistical difference between expression of DVL1, DVL2 and DVL3 and survival outcome. Increased expression of DVL1, DVL2 and DVL3 proteins in low- and high-grade serous ovarian carcinomas indicate that Dishevelled proteins may play an important role in pathogenesis of these carcinomas. Further studies should confirm the clinical relevance of these findings.

serous ovarian carcinoma ; Wnt signaling pathway ; DVL1 ; DVL2 ; DVL3

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