Part V: Detection of disseminated tumor cells in the bone marrow and blood of patients with epithelial ovarian cancer – micrometastasis project (PI: Janne Kærn MD PhD)

Background:

The presence of tumor cells in the bone marrow at the time of diagnosis has been shown to be an independent prognostic factor of disease-free (DFS) and overall (OS) survival in breast cancer (15). The amount of residual tumor after primary surgery is the most important prognostic factor in OC. Both the surgeon and tumor biology may influence the success in obtaining radical surgery. We have more than 10 years experience with detection of micrometastases in the bone marrow and blood, mostly through studies of breast, prostate and gastrointestinal cancer. Tumor cells are immunocytochemically detected, using an anti-pan-cytokeratin antibody. At the micrometastasis laboratory at the department of pathology at the Norwegian Radium
Hospital, this procedure is in routine use (16).

Aims and methodology of the proposed project:

In a previous study of 90 OC patients, we found micrometastases in 21% of cases, although the presence of micrometastases did not correlate with DFS or OS (17). The method used was based on DynabeadsTM, i.e., immunomagnetic selection using the epithelial-specific antibody MOC-31. We wish to perform a larger prospective study in order to examine the frequency and prognostic value of the presence of tumor cells in the bone marrow and blood of OC patients referred to our institution for primary treatment. Patients with an expected diagnosis of ovarian, tubal or peritoneal carcinoma who accept undergoing bone marrow (BM) and blood (B) aspirates and sign informed consent will be enrolled. Specimens will be examined for micrometastases at diagnose, prior to primary surgery and chemotherapy. A new BM and B aspiration will be taken 6 months after the end of primary therapy and at the date of first recurrence. The results for BM and B tests will be compared. In case no statistically significant differences will be found, we will substitute the BM test with the easier B test. Results from the analysis will be related to DFS, OS and classic prognostic factors. Treatment may be changed if detection of tumor cells in BM/B will be found to correlate with survival, following the model of breast cancer, in which patients with micrometastases get more aggressive therapy. In addition to prognostic value and elucidation of aspects of the metastatic process, detection of circulating tumor cells may be a potential tool for monitoring the course of the disease and therapy response for individual patients. We further wish to examine tumor cells in BM and B separately for various biological characteristics (stem cell phenotype, dormant cells, differences in metastatic potential, etc). We have to date enrolled 26 patients in this study.