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. 2009 Jan;112(1):185-91.
doi: 10.1016/j.ygyno.2008.09.021. Epub 2008 Oct 26.

Clinical significance of circulating tumor cells detected by an invasion assay in peripheral blood of patients with ovarian cancer

Tina Fan  1 , Qiang Zhao, John J Chen, Wen-Tien Chen, Michael L Pearl
Affiliations

Clinical significance of circulating tumor cells detected by an invasion assay in peripheral blood of patients with ovarian cancer

Tina Fan et al. Gynecol Oncol. 2009 Jan.

Abstract

Objectives: The invasive growth of circulating tumor cells (CTCs) propagates cancer metastasis. The aims of this study were to evaluate the association of invasive CTCs, detected by a novel cell invasion assay, with disease stage, CA-125 level and patient survival.

Methods: Peripheral blood samples from 71 patients undergoing evaluation for ovarian malignancy were assessed for the presence of invasive CTCs using a cell invasion assay that enriches and identifies tumor cells with a cell adhesion matrix (CAM). Invasive CTCs were identified as cells exhibiting CAM invasion (CAM+) and expressing standard epithelial markers (Epi+).

Results: 43 (60.6%) patients had detectable CTCs: 0/5 benign patients, 1/10 (10%) early stage, 39/52 (73.1%) late stage and 3/4 (75%) unstaged patients (p-value <0.001). CTC counts ranged from 0-149 CTCs/ml with stage III/IV patients exhibiting significantly higher mean counts (41.3 CTCs/ml) than stage I/II patients (6.0 CTCs/ml) and benign patients (0 CTCs/ml, p-value=0.001). A positive correlation between CTC count and CA-125 level was observed (Spearman correlation coefficient r=0.309, p-value=0.035). Kaplan-Meier curves revealed a significant decrease in disease-free survival in patients with detectable CTCs (median survival 15.0 months vs. 35.0 months, log-rank p-value=0.042). Tumor grade and tumor histology did not influence CTC detection.

Conclusions: Invasive CTCs can be detected in a majority of epithelial ovarian cancer patients and may predict shorter disease-free survival. Furthermore, higher CTC counts may reflect later stage disease and higher CA-125 levels.

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Conflict of interest statement

Conflict of Interest Statement:

Although we do not feel that the following information has biased our research in any capacity, we would like to disclose the following information:

Wen-Tien Chen is the founder of Vitatex Inc., the company who manufactures the cell invasion assay (Vita-Assay™) used in this work.

Tina Fan is the daughter-in-law of Wen-Tien Chen and served as a consultant to Vitatex Inc. for 9 months in 2006-2007. At the time she performed the work presented in this manuscript, she was no longer employed by Vitatex Inc., however her spouse maintains a position in the company.

Again, we would like to emphasize that despite these potential conflicts of interest, the utmost objectivity and adherence to the high ethical standards of scientific research were practiced in preparing this manuscript.

Figures

Figure 1
Figure 1
CTC detection by the CAM invasion assay. a) CTCs and hematologic cells from a stage IIIc ovarian cancer patient that ingested fluorescent CAM fragments (CAM+) and positive immuno-staining with epithelial cell lineage markers (Epi+). Arrows indicate CTCs in the identical field seen under different microscopic panels; hematologic cells are shown as color stained in red with antibody against CD45 in the lowest panel. b) Concordance experiment to test experimental variability of split samples analyzed under identical conditions.
Figure 2
Figure 2
CTCs by stage. a) CTC detection rates. Percentage of patients within a stage that had detectable CTCs. Absolute number of patients with detectable CTCs are given in (). b) Mean CTC counts. Error bars indicate SEM.
Figure 3
Figure 3
Overall Survival.
Figure 4
Figure 4
Disease-Free Survival.
See this image and copyright information in PMC

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