Correlation of genetic instability of nm23H1 gene to clinicopathologic features of epithelial ovarian carcinoma

Objective: Genetic instability, including microsatellite instability (MSI) and loss of heterozygosity (LOH), is the main reason for anti-oncogenes function maladjustment, and tumorigenesis. This research was to explore the correlation of genetic instability of nm23H1 gene to clinicopathologic features of epithelial ovarian carcinoma, and provide experimental basis for revealing the mechanism of nm23H1 gene function and tumor metastasis.

Methods: MSI and LOH of locus D17S396 in 25 specimens of epithelial ovarian carcinoma and relevant pericancerous tissues were detected by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) with ordinary silver staining. EnVision immuno-histochemistry and Leica-Qwin computer imaging techniques were used to assess the expression of nm23H1 protein.

Results: The detection rates of MSI and LOH of locus D17S396 in the 25 specimens of epithelial ovarian carcinoma were 16.00% and 24.00%, and the positive rate of nm23H1 protein was 56.00%. The frequency of LOH was significantly higher in the cases with lymph node metastasis than in those without metastasis (66.67% vs. 10.53%, P<0.01), and was significantly higher in the cases at FIGO stage III-IV than in those at stage I-II (50.00% vs. 11.76%, P<0.05). The positive rate of nm23H1 protein was significantly lower in the cases with lymph node metastasis than in those without lymph node metastasis (16.67% vs. 68.42%, P<0.05), and was significantly lower in the cases at FIGO stage III-IV than in those at stage I-II (25.00% vs. 70.59%, P<0.05). The expression intensity of nm23H1 protein had no correlation to clinicopathologic factors of epithelial ovarian carcinoma when analyzed by computer imaging techniques. The positive rate of nm23H1 protein was significantly lower in the cases with LOH of locus D17S396 than in those without LOH of locus D17S396 (0.00% vs. 73.68%, P<0.01).

Conclusions: The occurrence of LOH may be a molecular marker for the canceration of ovarian tissues. MSI and LOH of nm23H1 gene regulate the development of epithelial ovarian tumor through different pathways. LOH could inhibit the expression of nm23H1 in epithelial ovarian carcinoma.