Molecular Profiling and Prognostic Relevance of Circulating Tumor Cells in the Blood of Ovarian Cancer Patients at Primary Diagnosis and After Platinum-Based Chemotherapy

21085 Background: The impact of circulating tumor cells (CTC) in patients with primary breast cancer is still unclear. Primary systemic treatment (PST) allows the assessment of therapeutic efficacy in breast cancer patients without long follow-up periods. Here we present first results on the presence of CTC in peripheral blood of patients enrolled in the “GeparQuattro” study. Methods: This study incorporates three different chemotherapy approaches and additional Trastuzumab (Herceptin®) treatment for patients with HER-2/neu-positive tumors. Recruitment finished in November 2006 and not all patients have completed therapy yet. We used the CellSearch™ system to evaluate CTC before PST from 245 patients and after PST from 67 patients. CTC from 45 samples were also examined for HER-2/neu expression by immunocytochemistry in the CellSearch™ system. Results: Before PST we detected CTC in 54/245 patients (22%). CTC numbers in 7.5 mL blood ranged between 1 and 200 (mean 6.5). In 8 CTC-positive samples (3.3%) = 5 CTC were found. Her-2/neu-positive CTC were observed in 25/45 cases (55.6%). CTC could be detected in 7/67 patients (10.4%) after PST (1 or 2 CTC). Before and after PST blood was analyzed from 43 patients, 27 of them were CTC-negative at both time points. Ten initially CTC-positive cases were CTC-negative after PST whereas 6 cases were detected CTC-positive after PST although no CTC could be found before PST. Conclusions: With the CellSearch™ system CTC can be detected in non-metastatic breast cancer patients at primary diagnosis and also after PST. To our knowledge, this is the largest study evaluating the presence of CTC in this context. With the availability of response information from more patients, it will be possible to examine the correlation between the incidence of CTC and response as well as kinetics of HER-2/neu expression during Trastuzumab treatment. [Table: see text]

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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.

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ERCC1-expressing circulating tumor cells as a potential diagnostic tool for monitoring response to platinum-based chemotherapy and for predicting post-therapeutic outcome of ovarian cancer

Oncotarget ◽

10.18632/oncotarget.13286 ◽

2016 ◽

Vol 8 (15) ◽

pp. 24303-24313 ◽

Cited By ~ 12

Author(s):

Issam Chebouti ◽

Jan Dominik Kuhlmann ◽

Paul Buderath ◽

Stephan Weber ◽

Pauline Wimberger ◽

...

Keyword(s):

Ovarian Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Diagnostic Tool ◽

Therapeutic Outcome ◽

Platinum Based Chemotherapy ◽

Monitoring Response

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Serum calretinin as a predictor for recurrence and overall survival in ovarian cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e17033 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e17033-e17033

Author(s):

Pauline Wimberger ◽

Simon Passek ◽

Theresa Link ◽

Yana Vassileva ◽

Michael Kramer ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Liquid Biopsy ◽

Calcium Binding ◽

Tumor Resection ◽

High Volume ◽

Primary Diagnosis ◽

Platinum Resistance ◽

Serum Samples ◽

Platinum Based Chemotherapy

e17033 Background: Calretinin (CRT) is a calcium-binding protein, controlling intracellular calcium signaling. Besides its prominent expression in neurons, CRT has diagnostic implications in cancer, particularly in mesothelioma. In a recent liquid biopsy approach, plasma CRT level has been suggested for pre-diagnostic detection of mesothelioma. CRT is also expressed in serous ovarian cancer in about 23% of cases; however, clinical relevance of serum CRT is completely unknown and shall therefore be analyzed, herein. Methods: Serum calretinin (sCRT) was determined by calretinin enzyme-linked immunoabsorbent assay (DLD-Diagnostika GmbH, Hamburg) in a total of 380 serum samples from 134 ovarian cancer patients (thereof n = 115 (86%) with FIGO III or IV), including samples at primary diagnosis and at 4 follow-up reading points in the course of adjuvant treatment. Results: sCRT levels were significantly increased in ovarian cancer patients compared to healthy controls (ED = 0.3ng/ml, p < 0.001) and enabled an accurate discrimination between ovarian cancer and controls (AUC = 0.85). High sCRT levels at primary diagnosis predicted suboptimal debulking surgery without achieving macroscopically complete tumor resection (p < 0.001) and were associated with advanced FIGO-stage (p < 0.001) and high volume of ascites (p < 0.001). Increased sCRT levels at primary diagnosis were an independent predictor of poor PFS (HR:1.99, p = 0.018) and also indicated poor OS (HR:2.49, p = 0.008). Increased sCRT levels before and after platinum-based chemotherapy were independent predictors of poor OS (HR:15.4, p = 0.01; HR:5.59, p = 0.026). Moreover, elevated sCRT levels at primary diagnosis indicated platinum-resistance (p = 0.002). Conclusions: This is the first study, suggesting sCRT as an innovative liquid biopsy marker for ovarian cancer by showing its independent prognostic relevance and its association with primary platinum-resistance.

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Abstract 594: Image-based identification of single circulating tumor cells in ovarian cancer patients for genomic analysis

10.1158/1538-7445.am2021-594 ◽

2021 ◽

Author(s):

Carolin Salmon ◽

Janina Levermann ◽

Paul Buderath ◽

Jan Dominik Kuhlmann ◽

Pauline Wimberger ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Genomic Analysis

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