PURPOSE: To investigate chemosensitivity with an adenosine triphosphate-based chemotherapy response assay in patients with epithelial ovarian or peritoneal cancer according to tumor histology, grade, and disease status. MATERIALS AND METHODS: One hundred specimens were collected during primary or secondary debulking from 67 patients with primary ovarian cancer, 24 patients with recurrent ovarian cancer, 5 patients with primary peritoneal cancer, and 4 patients with recurrent peritoneal cancer; samples were collected between August 2006 and June 2009. Tumor cells were isolated and cultured for 48 hours in media containing chemotherapy. The chemosensitivity index (CI) was calculated as 300 minus the sum of the cell death rate at 0.2x, 1x, and 5x drug concentrations, and the CI values were compared. RESULTS: CI values were obtained from 93 of 100 patients. The most active agents against primary disease were ifosfamide and paclitaxel. For primary serous adenocarcinoma, paclitaxel and irinotecan were the most active, followed by ifosfamide. For clear cell carcinoma, ifosfamide was the most active, followed by paclitaxel and irinotecan. Although not statistically significant, the CIs of cisplatin, carboplatin, paclitaxel, and docetaxel decreased as tumor grade increased. In 14 cases of recurrent disease, paclitaxel was the most active, followed by ifosfamide and cisplatin. CONCLUSION: Ifosfamide and paclitaxel were the most active drugs for primary and recurrent disease. Therefore, we recommend further clinical studies to confirm the efficacy of paclitaxel, ifosfamide, and cisplatin combination chemotherapy for recurrent and primary ovarian cancer.
Adenocarcinoma, Clear Cell/*drug therapy/metabolism/pathology ; Adenosine Triphosphate/*metabolism ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Camptothecin/administration & dosage/analogs & derivatives ; Carboplatin/therapeutic use ; Cisplatin/administration & dosage ; Drug Resistance, Neoplasm ; Drug Screening Assays, Antitumor/methods ; Female ; Humans ; Ifosfamide/administration & dosage ; Middle Aged ; Neoplasm Recurrence, Local/*drug therapy ; Neoplasms, Glandular and Epithelial/*drug therapy/metabolism/pathology ; Ovarian Neoplasms/*drug therapy/metabolism/pathology ; Paclitaxel/therapeutic use ; Peritoneal Neoplasms/*drug therapy/metabolism/pathology ; Predictive Value of Tests ; Sensitivity and Specificity ; Taxoids/administration & dosage

OBJECTIVE: Epithelial cell adhesion molecule (EpCAM) has experienced a renaissance lately as a binding site for targeted therapy as well as a prognostic marker in epithelial malignancies. Aim of this study was to study EpCAM as a potential prognostic marker in epithelial ovarian cancer (EOC). METHODS: EpCAM expression was assessed by immunohistochemistry on paraffin-embedded primary EOC-tissue samples. EpCAM overexpression was defined as an expression of EpCAM of 76% to 100%. Tissue samples and clinical data were systematically collected within the international and multicenter "Tumorbank Ovarian Cancer" network. RESULTS: Seventy-four patients, diagnosed with EOC between 1994 and 2009, were included in the study (median age, 56 years; range, 31 to 86 years). The majority of the patients (81.1%) presented with an advanced stage International Federation of Gynecology and Obstetrics (FIGO) III/IV disease. Histology was of the serous type in 41 patients (55.4%), endometrioid in 19 (25.6%), and mucinous in 14 (19%). EpCAM was overexpressed in 87.7%. Serous tumors overexpressed EpCAM significantly more often than mucinous tumors (87.8% vs. 78.6%, p=0.045); while no significant difference was noted between the other histological subgroups. EpCAM overexpression was significantly associated with a better progression free survival and higher response rates to platinum based chemotherapy (p=0.040 and p=0.048, respectively). EpCAM was identified as an independent prognostic marker for overall survival (p=0.022). CONCLUSION: Our data indicate a significant association of EpCAM overexpression with a more favorable survival in EOC-patients. Serous cancers showed a significant EpCAM overexpression compared to mucinous types. Larger multicenter analyses are warranted to confirm these findings.
Adult ; Aged ; Aged, 80 and over ; Antigens, Neoplasm/*metabolism ; Antineoplastic Agents/*therapeutic use ; Carboplatin/therapeutic use ; Cell Adhesion Molecules/*metabolism ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Proteins/metabolism ; Neoplasm Staging ; Neoplasms, Glandular and Epithelial/*diagnosis/drug therapy/pathology ; Organoplatinum Compounds/*therapeutic use ; Ovarian Neoplasms/*diagnosis/drug therapy/pathology ; Paclitaxel/therapeutic use ; Prognosis ; Tissue Banks ; Treatment Outcome ; Tumor Markers, Biological/*metabolism