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.
Chen
Yi-Jen
YJ
Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan.
Yuan
Chiou-Chung
CC
Chow
Kuan-Chih
KC
Wang
Peng-Hui
PH
Lai
Chiung-Ru
CR
Yen
Ming-Shyen
MS
Wang
Liang-Shun
LS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D010088:Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004273:DNA, Neoplasm; D012333:RNA, Messenger; D010088:Oxidoreductases; C048338:trans-1,2-dihydrobenzene-1,2-diol dehydrogenase; D002945:Cisplatin