Download Circulating tumor cell (CTC) characterization in metastatic breast

Circulating tumor cell (CTC) characterization in metastatic breast cancer
An important part of cancer progression is when the primary tumor starts to release tumor cells into
the blood circulation. This is the first step towards metastatic disease and is thus of immense
importance for disease development. It is well known that the number of cancer cells that can be
found in the circulation (circulating tumor cells=CTCs) is of importance for patient prognosis. We
have a method called CellSearch® (Janssen Diagnostics) that can be used to draw out CTCs from
blood samples and enumerate CTCs using immunofluorescence. This method is used in a number of
clinical studies here in Lund today and it is the most established method to study CTCs worldwide.
In a previous study we have found that presence of CTCs that form clusters in the blood of patients
with metastatic breast cancer is a significant sign of bad prognosis. The same is true for CTCs with
apoptotic features (i.e. dying cancer cells in the blood). Both of these characteristics were only
important when found at time-points when the patients had started their therapy.
The aim of the present study is to continue with morphologic characterization of CTCs in patients
with metastatic breast cancer. CTC size, shape, cytokeratin staining intensity and nuclear-tocytoplasmic ratio will be investigated in relation to prognosis, metastatic site, and breast cancer
subtype. We hypothesize that small, round CTCs are more aggressive and might represent a more
cancer stem cell like phenotype.
Methods: Serial samples from patients with metastatic breast cancer will be investigated and the
student will work with data from the ongoing CTC-MBC study (ethical permission EPN 2010/135).
Blood samples have been drawn at baseline, 1-3 and 6 months of treatment and will be evaluated for
CTC size, shape, nuclear-to-cytoplasmic ratio and staining intensity using the public domain JAVAbased image processing program ImageJ. Png formatted images from the CTC gallery will be used for
the measurements and the perimeter, cross sectional area, longest and shortest diameter, circularity
(how much the cell shape differ from a perfect circle) and intensity for all CTC and their
corresponding nuclei. In a pilot study, CTCs and their corresponding nuclei have been measured in
the baseline sample for each of 39 patients with ≥5 detected CTCs.
Supervisors: Kristina Aaltonen (PhD) och Sara Jansson (MD, PhD-student)