In vitro chemoresistance and biomarker profiles are unique for histologic subtypes of epithelial ovarian cancer.
OBJECTIVE
To determine whether there is a relationship between histologic subtype of epithelial ovarian cancer and chemoresistance, we evaluated ovarian carcinomas of six histologic subtypes and correlated histology with in vitro drug response. Biomarker profiles (p53, Her-2 neu, and EGFR) were also evaluated to determine if their expression patterns were associated with histology.


METHODS
In vitro drug response profiles for different histologic subsets of epithelial ovarian carcinomas exposed to standard relevant chemotherapy agents were determined in the Extreme Drug Resistance assay (EDR). Immunohistochemistry techniques were employed to determine biomarker expression.


RESULTS
Of 5195 referred serial cases of epithelial ovarian cancer, there were 2660 papillary serous, 303 endometrioid, 142 mucinous, 102 clear cell, 952 undifferentiated carcinomas, and 42 tumors of low malignant potential. For the samples as a whole, the incidences of extreme drug resistance to the tested chemotherapeutic agents were cisplatin 10%, carboplatin 16%, cyclophosphamide 16%, doxorubicin 40%, gemcitabine 21%, paclitaxel 22%, and topotecan 13%. When compared to papillary serous tumors, mucinous tumors were more frequently resistant to cisplatin (10% vs. 18%) but less frequently resistant to topotecan (13% vs. 5%) and doxorubicin (42% vs. 16%). Endometrioid tumors were less resistant to cisplatin (10% vs. 6%) and doxorubicin (42% vs. 20%). Clear cell and undifferentiated tumors had the lowest rates of EDR to paclitaxel (13% and 18%) and cyclophosphamide (7% and 11%), while borderline tumors showed high rates of EDR to these agents (52% and 63%, respectively). With respect to biomarker profiles, mP53 was detected in 46%, Her-2 neu in 16%, and EGFR in 30% of the cases evaluated. As compared to all other subtypes, clear cell carcinomas had significantly higher Her-2 neu expression (19%). Relative to papillary serous carcinomas, borderline tumors exhibited significantly lower rates of mP53 expression (60% vs.17%).


CONCLUSIONS
We found significant differences in the frequencies of extreme drug resistance to chemotherapeutic agents and biomarker expression among histologic subtypes of epithelial ovarian cancer. The data collected in this investigation may provide a guide for stratification of patients entering clinical trials based on histology and biomarker expression.
Cloven
Noelle Gillette
NG
University of California Irvine, Orange, CA 92868, USA.
Kyshtoobayeva
Ainura
A
Burger
Robert A
RA
Yu
Ing Ru
IR
Fruehauf
John P
JP
D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004847:Epithelial Cells / Q000473:pathology; D066246:ErbB Receptors / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D010051:Ovarian Neoplasms / Q000145:classification* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53