title: Differences of chemoresistance assay between invasive micropapillary/low-grade serous ovarian carcinoma and high-grade serous ovarian carcinoma.
abstract: The objective of this study was to evaluate the pattern of chemoresistance in invasive micropapillary/low-grade serous ovarian carcinoma (invasive MPSC/LGSC) and high-grade serous ovarian carcinoma (HGSC) according to extreme drug resistance (EDR) assay testing. Surgical specimens of 44 recurrent ovarian cancer patients harvested at the time of cytoreductive surgery between August 1999 and February 2004 were identified retrospectively from the tumor registry database. Thirteen patients (29.5%) had recurrent invasive MPSC/LGSC and 31 (70.5%) patients had recurrent HGSC. Eight drugs were evaluated; EDR assay results were compared between LGSC and HGSC groups using Fisher exact tests and exact logistic regression models. Compared to HGSC, invasive MPSC/LGSC were more likely to manifest EDR to the drugs paclitaxel (69% vs 14%, P < 0.001), carboplatin (50% vs 17%, P= 0.05), cyclophosphamide (40% vs 23%, P= 0.41), gemcitabine (36% vs 19%, P= 0.40), and cisplatin (33% vs 28%, P= 0.72) and less likely to be resistant to etoposide (0% vs 44%, P= 0.007), doxorubicin (8% vs 45%, P= 0.03), and topotecan (8% vs 21%, P= 0.65). Exact logistic regression estimates revealed that invasive MPSC/LGSC patients had significantly increased probabilities of paclitaxel resistance odds ratio (OR) = 12.5 (95% CI: 2.3-100.0), P= 0.001 and carboplatin resistance OR = 4.8 (95% CI: 0.9-25.0), P= 0.07, while the HGSC cases were more likely to be resistant to etoposide OR = 12.1 (95% CI: 1.7-infinity), P=0.009 and doxorubicin OR = 8.6 (95% CI: 1.0-413.7), P= 0.05. In this retrospective analysis, patients with recurrent invasive MPSC/LGSC were more likely to manifest EDR to standard chemotherapy agents (platinum and paclitaxel). These observations may help to guide chemotherapeutic decision making in these patients if confirmed in a large-scale study.
authors.affiliation: Kelly Gynecology Oncology Service, Department of Gynecology and Obstetrics, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA. asantil1@jhmi.edu
authors.forename: A
authors.initials: A
authors.lastname: Santillan
authors.forename: Y W
authors.initials: YW
authors.lastname: Kim
authors.forename: M L
authors.initials: ML
authors.lastname: Zahurak
authors.forename: G J
authors.initials: GJ
authors.lastname: Gardner
authors.forename: R L
authors.initials: RL
authors.lastname: Giuntoli
authors.forename: I M
authors.initials: IM
authors.lastname: Shih
authors.forename: R E
authors.initials: RE
authors.lastname: Bristow
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D018283:Cystadenocarcinoma, Papillary / Q000188:drug therapy* / Q000473:pathology*; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy* / Q000473:pathology*; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D017239:Paclitaxel / Q000008:administration & dosage; D012189:Retrospective Studies
chemical_list: D017239:Paclitaxel; D002945:Cisplatin