Circulating Tumor Cell Detection

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Looking at the cancer literature reveals that most cancer patients perish due to dissemination of cells from the primary site and not from the primary tumor itself. The metastases formed in various locations in the body are the most dangerous sequelae of the cancer and ultimately lead to the death of the patient.

Recently, much effort has been devoted to the detection of cancer cells circulating freely in the patient’s blood stream on their way to forming these metastases, the so-called Circulating Tumor cells or CTCs.

CTCs are extremely rare and present as only 1-2 cells / ml of blood. A ml of blood contains billions of red blood cells and millions of white blood cells. Thus, it is necessary to enrich the analyzed sample in order to have enough cells to submit to the assay

One method of enrichment involves using antibodies against epithelial cell adhesion molecule (EpCAM) tagged with magnetic particles which then are separable from the non-coupled molecules through the application of a magnetic field. Epithelial cells are distinguished from leucocytes using fluorescent labeled antibodies against the leucocytes (CD-45 Ab) as well as cytokeratins 8, 18 and 19.

Yet another method for sample enrichment uses a combination of multiple antibodies attached to posts arranged to create MEMS microfluidic channels through which the cells flow. Cells can then be evaluated by morphological, immunohistochemical or fluorescence in situ hybridization to assess their status.

The transparent microfluidic chambers ~50 microns in depth and contain roughly 9,000 posts, in a volume of about 24 microliters.

Most of the systems used for these assays rely on microscopy and fuorescence and are therefore, prime candidates for the use of sensitive scientific-grade CCD cameras.

The DVC-2000 and the DVC-1500 are ideally suited to applications such as these. The performance combination of speed, sensitivity and large field of view makes the DVC-2000 especially useful for fluorescence microscopy applications.

References

Abd El-Rehim DM, Pinder SE, Paish CE, et al. Expression of luminal and basal cytokeratins in human breast carcinoma. J Pathol. 2004;203:661-671

Allard WJ, Aquino A, Prete SP, Balduzzi A, et al. A novel method for monitoring response to chemotherapy based on the detection of circulating tumor cells: a case report. J Chemother. 2002;14:412-416.

Armstrong A, Eck S. EpCAM: A new therapeutic target for an old cancer antigen. Cancer Biology & Therapy. 2003;2:320-326.

Berrepoot LV, Mehra N, Vermaat JS, et al. Increased levels of viable circulating endothelial cells are an indicator of progressive disease in cancer patients. Ann Oncol. 2004;15:139-145.

Cristofanilli M, Budd T, Ellis M, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004;351:781-791.

Gaforio JJ, Serrano MJ, Sanchez-Rovira P, et al. Detection of breast cancer cells in the peripheral blood is positively correlated with estrogen-receptor status and predicts for poor prognosis. Int J Cancer. 2003;107:984-990.

Katoh M, Neumaier M, Nezam R, et al. Correlation of circulating tumor cells with tumor size and metastatic load in a spontaneous lung metastasis model. Anticancer Res. 2004;24:1421-1425.

Matera J, Miller MC, et al. Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res. 2004;10:6897-6904.

Molnar B, Sipos F, Galamb O, et al. Molecular detection of circulating cancer cells. Dig Dis. 2003;21:320-325.

Osta W, Chen Y, Mikhitarian K, et al. EpCAM is overexpressed in breast cancer and is a potential target for breast cancer gene therapy. Cancer Research. 2004;64:5818-5824.

Weigelt B, Bosma AJ, Hart AA, Rodenhuis S, et al. Marker genes for circulating tumour cells predict survival in metastasized breast cancer patients. Br J Cancer. 2003;88:1091-1094.