Abstract
Objectives. 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.
Keywords
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Article info
Publication history
Received:
March 24,
2003
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© 2003 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
