Up-regulation of cadherin 17 and down-regulation of homeodomain protein CDX2 correlate with tumor progression and unfavorable prognosis in epithelial ovarian cancer.

OBJECTIVE: Cadherin 17 (CDH17), belonging to the 7D-cadherin superfamily, represents a novel oncogene, which is involved in tumor invasion and metastasis. Its expression has been demonstrated to be regulated by caudal-related homeobox transcription factor CDX2. The roles of 2 biomarkers have been conflictingly explained. Therefore, the aims of this study were to investigate the expression patterns of CDH17 and CDX2 in human epithelial ovarian cancer (EOC) and to evaluate the clinical significance of these 2 markers in the progression and prognosis of EOC.

METHODS: CDH17 and CDX2 expressions in 182 paraffin-embedded EOC specimens were detected by immunohistochemical staining. Associations of their expression with clinical pathological factors and overall survival were statistically evaluated.

RESULTS: Compared with normal surface ovarian epithelium tissues, CDH17 expression was upregulated and CDX2 expression was downregulated in EOC tissues. There was a negative correlation between CDH17 and CDX2 expression in EOC tissues (r = -0.76, P = 0.001). Tumors with high CDH17 expression were more likely to have advanced stage (P = 0.01) and higher grade (P = 0.03). Patients with low CDX2 expression were more frequently to be at the advanced stage of disease (P = 0.01). In addition, univariate analysis indicated that the patients with high CDH17 expression correlated with poor prognosis in patients with EOC (P = 0.001), as opposed to CDX2 (P = 0.003). Especially, the survival rate of patients with EOC with CDH17-high/CDX2-low expression was the lowest (P < 0.001). Multivariate statistical analysis showed that the conjoined expression of CDH17/CDX2 was an independent prognostic indicator of EOC (P = 0.01).

CONCLUSIONS: Our data suggest that both the up-regulation of CDH17 and the down-regulation of CDX2 may be associated with the advanced stage of EOC. A conjoined detection of CDH17/CDX2 expression may be associated with unfavorable prognosis in patients with this disease.