Influence of platinum-based chemotherapy on disseminated tumor cells in blood and bone marrow of patients with ovarian cancer.
OBJECTIVE
We evaluated (1) the prevalence of disseminated tumor cells (DTC) before and after first-line chemotherapy with carboplatin and paclitaxel in the bone marrow (BM) and peripheral blood (PB) of 57 patients with primary ovarian cancer and (2) the coexpression of the epithelial antigen EpCAM on DTC including the determination of apoptotic cells.


METHODS
DTC were detected by immunocytochemistry applying the anti-cytokeratin (CK) antibody A45-B/B3. For double-labeling of DTCs, the antibodies M30 (apoptosis), HEA-125-FITC/Ber-EP4-FITC (EpCAM) were used.


RESULTS
Before chemotherapy, we identified DTC in 12/57 PB samples (21%) with a median number of 2 cells/20 ml (range 1-8) and in 25/46 BM samples (54%) with a median number of 5 cells/9x10E6 BM cells (range 1-28). Analysis of DTC in PB and BM before and after therapy was performed in 30 patients. In this subgroup, we identified DTC in 5/30 PB samples (16%) and in 15/30 BM samples (50%) before chemotherapy. After chemotherapy, DTC in PB were only detected in one patient but in the BM of 15/30 patients (50%). After chemotherapy, BM analysis revealed evidence that no DTC were detectable any longer in 9 patients, no significant change in DTC was documented in 14 patients and a significant enhancement of DTC was shown in 10 patients, including 8 patients who had no DTC before chemotherapy. DTC, still present after chemotherapy, co-expressed EpCAM and were non-apoptotic. In a univariable analysis, patients with a marked increase of DTC showed a significantly reduced PFS (p=0.041). A corresponding multivariable Cox regression analysis was not feasible due to the limited number of events. No correlation of DTC in BM and PB was found with patient's and tumor characteristics.


CONCLUSIONS
DTC were present in 50% of patients after first-line chemotherapy in ovarian cancer. It has to be considered whether patients with persisting EpCAM/CK-positive BM cells probably might benefit from an additive immunotherapy e.g. targeting EpCAM.
Wimberger
Pauline
P
Department of Gynecology and Obstetrics, University of Duisburg-Essen, Hufelandstrasse 55, D-45122 Essen, Germany.
Heubner
Martin
M
Otterbach
Friedrich
F
Fehm
Tanja
T
Kimmig
Rainer
R
Kasimir-Bauer
Sabine
S
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001707:Biopsy, Needle; D001853:Bone Marrow / Q000187:drug effects* / Q000473:pathology*; D001856:Bone Marrow Examination; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D017671:Platinum Compounds / Q000008:administration & dosage; D015995:Prevalence; D011446:Prospective Studies; D016896:Treatment Outcome
D017671:Platinum Compounds