Abstract
Clinical studies have demonstrated that circulating tumor cells (CTCs) are present in the blood of cancer patients with known metastatic disease across the major types of epithelial malignancies. Recent studies have shown that the concentration of CTCs in the blood is prognostic of overall survival in breast, prostate, colorectal, and non-small cell lung cancer. This study characterizes CTCs identified using the high-definition (HD)-CTC assay in an ovarian cancer patient with stage IIIC disease. We characterized the physical properties of 31 HD-CTCs and 50 normal leukocytes from a single blood draw taken just prior to the initial debulking surgery. We utilized a non-interferometric quantitative phase microscopy technique using brightfield imagery to measure cellular dry mass. Next we used a quantitative differential interference contrast microscopy technique to measure cellular volume. These techniques were combined to determine cellular dry mass density. We found that HD-CTCs were more massive than leukocytes: 33.6 ± 3.2 pg (HD-CTC) compared to 18.7 ± 0.6 pg (leukocytes), p < 0.001; had greater volumes: 518.3 ± 24.5 fL (HD-CTC) compared to 230.9 ± 78.5 fL (leukocyte), p < 0.001; and possessed a decreased dry mass density with respect to leukocytes: 0.065 ± 0.006 pg/fL (HD-CTC) compared to 0.085 ± 0.004 pg/fL (leukocyte), p < 0.006. Quantification of HD-CTC dry mass content and volume provide key insights into the fluid dynamics of cancer, and may provide the rationale for strategies to isolate, monitor or target CTCs based on their physical properties. The parameters reported here can also be incorporated into blood cell flow models to better understand metastasis.
Highlights
Ovarian cancer is the most lethal gynecological cancer and the fifth leading cause of cancer death among women in the United States
First we investigated the ability of the transport of intensity equation (TIE) to perform phase retrieval at the diffraction limit of the microscope by evaluating the algorithm on 0.11 μm diameter spheres subject to Köhler illumination at an numerical aperture (NA) = 0.33
Flowdependent interactions with red blood cells (RBCs) in the vessels of the microcirculation give rise to the prevalence of less dense cells along the periphery of the vessel wall, a phenomenon known as margination (Goldsmith and Spain, 1984)
Summary
Over 90% of stage I patients with ovarian cancer can be cured with the current standard of care: tumor resection followed by platinum and taxane based chemotherapy. Only 20% of ovarian cancers are detected in stage I (Bast et al, 2009). This is due in part to the anatomic location of the ovaries deep within the pelvis, the absence of tumor-specific symptoms (Lim et al, 2012) and a lack of effective serum markers that correlate with early disease progression (Anderson et al, 2010; Urban et al, 2011). The development of sensitive and specific diagnostic techniques for ovarian cancer is imperative to enhance the treatment outcomes of this disease. The enumeration and physical characterization of circulating tumor cells (CTCs) represents a new strategy to monitor the dynamics of tumor burden and potentially gain insight into the hematogenous transport of CTCs to other locations in the body
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
