Overexpression of dihydrodiol dehydrogenase is associated with cisplatin-based chemotherapy resistance in ovarian cancer patients.
OBJECTIVE: Results of a recent study on human ovarian cancer cell lines indicated that overexpression of dihydrodiol dehydrogenase ( DDH) was associated with resistance to cisplatin and disease progression. We examined the relationships between DDH expression and chemotherapy resistance in ovarian cancer patients. METHODS: Using immunohistochemistry, expression of DDH was measured in 41 patients with epithelial ovarian cancers. All patients underwent primary debulking surgery, followed with six cycles of cisplatin-based chemotherapy. Normal ovarian tissues were obtained from patients with benign gynecologic diseases (n = 14). Expression of DDH was confirmed by reverse transcription-polymerase chain reaction. The correlation between DDH expression and clinico-pathological parameters was analyzed by statistical analysis. Difference of progression-free survivals between different groups was compared by a log-rank test. RESULTS: Eighteen ovarian cancer samples (43.9%) expressed DDH at a moderate to strong level. This marked a significant difference from the negligible expression (1/14, 7.1%) found in the control group (P = 0.02). Of interest, the clear cell adenocarcinoma revealed DDH overexpression (75%) and mucinous adenocarcinoma revealed low DDH expression (16.7%), although DDH expression did not show any significant variation according to different histotypes. DDH overexpression was found in a statistically significantly higher percentage of cisplatin-resistant cases (n = 8/11; 72.7%) than in cisplatin-sensitive cases (n = 9/27; 33.3%) (P = 0.037). Using multivariate analysis, only DDH retained as an independent role in predicting a poor chance of response to cisplatin-based treatment. DDH overexpression cases (median 12 months, 95% confidence interval 4-20) demonstrated a shorter progression-free survival than DDH-negative cases (median 28 months, 95% confidence interval 23-33), but this result did not reach the statistical significance (P = 0.1742). In the advance stage, the DDH-positive group has a shorter PFS as compared with DDH-negative group, and this result closely approaches the statistical significance (P = 0.0669). CONCLUSIONS: DDH is expressed in a high percentage of primary ovarian tumors and its expression may be associated with cisplatin-based chemotherapy resistance. The possible prognostic role of DDH in ovarian carcinoma deserves further study.[1]References
- Overexpression of dihydrodiol dehydrogenase is associated with cisplatin-based chemotherapy resistance in ovarian cancer patients. Chen, Y.J., Yuan, C.C., Chow, K.C., Wang, P.H., Lai, C.R., Yen, M.S., Wang, L.S. Gynecol. Oncol. (2005) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
