The Ohio State University uses two different approaches to visualize circulating tumor cells (CTCs) and other unusual circulating cells, with both epithelial and hematopoietic characteristics in metastatic breast cancer (mBC) for their new research.

The researchers presented the study results during a poster session at the American Association for Cancer Research Annual Meeting 2012 in Chicago, Ill.

Researchers with The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute used immunocytochemistry and flow cytometry in order to examine enriched blood samples taken from individuals suffering from mBC. The study was supported in part by pilot funding from the Ohio State Center for Clinical and Translational Science (CCTS).

Maryam B. Lustberg, M.D., MPH, study investigator and assistant professor of internal medicine at The Ohio State University College of Medicine, explained:

“By utilizing a negative depletion process we were able to identify rare CTCs that are often overlooked by current methods of study. While more information is needed to understand the clinical significance of these cells, with further research, it’s possible these atypical cells could influence prognoses and treatments in the future.”

The researchers defined a CTC as a nucleated cell, which is cytokeratin positive and CD45 negative and positive for epithelial cell adhesion activating molecule (EpCAM). Trained specialists are able to identify CTCs by using fluorescently stained slides, known as EpCAM enrichment technology, however this process only identifies EpCAM positive CTCs.

Lustberg, explained:

“Some of the most aggressive forms of cancer, including triple negative breast cancer (TNBC), downregulate EpCAM and have high numbers of EpCAM negative CTCs, cells that would be missed by the most commonly utilized technologies. The results of this study support the theory that there is a heterogeneous population of circulating cells in the blood of cancer patients which may hold clues regarding the metastatic process.”

In addition, the team identified abnormal double positive cells. These cells have only been identified in individuals with cancer. The double positive cells tested positive for CD45 and cytokeratin, indicating that the cells have cancer and normal blood characteristics. Researchers have previously believed that this combination was impossible.

In prior investigations double positive cells have been looked at anecdotally although researchers disregarded them as artifacts of the testing process. However, results from this study indicate that the characteristics of these double positive cells may be more meaningful than researchers previously believed.

Jeffery Chalmers, Ph.D., study researcher, professor in Ohio State’s Department of Chemical and Biomolecular Engineering and director of the Cytometry Shared Resource at the Center for Scientific Review, said:

“The presence of these double positive cells points to an unusual mutation taking place in the blood of cancer patients.

Our team is currently working with researchers in the field of cell biology and immunology to further characterize the cells and understand their implications in the field of cancer research.”

The study included 40 women aged between 28 and 78, who were either had TNBC (47%) or were estrogen receptor positive (52%). Patients with mBC aged 18+ who had less than two previous lines of systemic therapy were eligible to enroll in the study. All participants had bone and organ metastases and 60% had received two previous lines of chemotherapy. The researchers also enrolled healthy volunteers without a known diagnosis of malignancy.

In order to characterize the CTCs and double positive cells identified in the study, the researchers are currently conducting follow-up studies.

Written By Grace Rattue