Disseminated tumor cells in bone marrow of cancer patients

21013 Background: The presence of disseminated tumor cells (DTC) in bone marrow (BM) of primary breast cancer patients is associated with poor prognosis. These patients may benefit from adjuvant endocrine therapy since cytotoxic agents are not able to completely eliminate DTCs as previously shown. Only patients with hormone receptor positive breast cancer are eligible for hormonal treatment. The ERa status is routinely defined in primary tumor tissue. However, the ERa status of DTC may differ compared to the primary tumor. Therefore, the aims of this study were (1) to determine the ERa status of DTC in BM of breast cancer patients, (2) and to compare the ERa status of DTC and corresponding primary tumors. Methods: BM aspirates from 251 primary breast cancer patients were included into the study. A double immunofluorescence staining procedure was established for the identification of cytokeratin-positive (CK)/ERa positive cells. ERa status of the primary tumor was immunohistochemically assessed using the same antibody against ERa. Results: In 105 of 251 (42%) breast cancer patients CK-positive cells could be detected in BM. The number of detected cells ranged between 1 and 13 / cells per 2*106 mononuclear cells. Disseminated tumor cells demonstrated ERa positivity in 13 (12%) of these 105 patients. The ERa expression on DTC was heterogeneous in 10 of 13 (79%) patients. Concordance rate of ERa status between primary tumor and DTC was 27%. Only 11 of 83 patients with ER a positive tumors had also ERa positives DTC. Conclusions: (1)The hormone receptor status between primary tumor and corresponding DTC is disconcordant. (2)This discrepancy may explain the rate of non-responders to adjuvant endocrine therapy despite ER-positive primary tumors. (3)These patients may benefit from adjuvant therapy regimens based on antibody strategies or bisphosphonates. No significant financial relationships to disclose.

Download Full-text

Role of an EpCAM auto-antibody in ovarian cancer patients with special regard to disseminated tumor cells in bone marrow

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e16557 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e16557-e16557

Author(s):

M. Heubner ◽

S. Kasimir-Bauer ◽

D. Errico ◽

D. Herlyn ◽

R. Kimmig ◽

...

Keyword(s):

Ovarian Cancer ◽

Bone Marrow ◽

Cancer Patients ◽

Tumor Cells ◽

Disseminated Tumor Cells ◽

Healthy Controls ◽

Line Treatment ◽

First Line ◽

Platinum Based Chemotherapy ◽

First Line Treatment

e16557 Background: EpCAM is a tumor associated antigen which is frequently expressed in ovarian cancer. Recently, an autoantibody (AAB) against EpCAM has been identified in ovarian cancer patients. Autoantibodies are immunogene factors and might be of prognostic importance. We showed that disseminated tumor cells (DTC) in bone marrow carry the EpCAM antigen on their surface and correlate with poorer progression free survival (PFS). Here, we evaluated whether EpCAM-AABs have an impact on clinical parameters or the presence of DTC in ovarian cancer patients. Methods: EpCAM-AABs were determined in sera of 28 healthy voluntary age matched females and 62 patients with primary epithelial ovarian cancer before and after platinum-based chemotherapy using a recombinant EpCAM-epitope for antibody- detection by ELISA technique. Mean follow up time was 13 months. DTC in BM were detected by immunocytochemistry applying the pan cytokeratin antibody A45-B/B3. All samples exceeding the mean antibody titer of healthy controls plus 2 standard deviations were considered positive. Results: The antibody titer of healthy controls was 0.061 + 0.015. Using a cut-off value of 0.091, we found 9/62 (15%) ovarian cancer patients to be positive for EpCAM-AABs after first-line treatment. Interestingly, no positive AAB-titers were seen before therapy. Using the paired T-Test, we noted a significant posttherapeutic increase of AABs (CI 0.95, p < 0.0001). Analysis of PFS, FIGO stage, resection status, grading, age, sensitivity to platinum based chemotherapy and DTC did not reveal significant associations with positive EpCAM-AAB titers. Conclusions: The clinical course of ovarian cancer patients and the prevalence of DTC were not altered by EpCAM-AABs. Interestingly, we observed an increase of antibody-levels after first-line treatment. For further validation, we intend to extend our patient collective. In future, it might also be interesting to investigate the impact of AABs on response to targeted therapies against EpCAM. No significant financial relationships to disclose.

Download Full-text