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Circulating Tumor Cells in Perioperative Esophageal Cancer Patients: Quantitative Assay System and Potential Clinical Utility

Authors' Affiliations: ¹ MOE Key Laboratory of Analytical Chemistry for Life Science, Department of Chemistry, Nanjing University; ² Tumor Hospital of Jiangsu Province; and ³ Center of Clinical Laboratory Science and Department of Surgery, Nanjing, P.R. China

Requests for reprints: Huangxian Ju, MOE Key Laboratory of Analytical Chemistry for Life Science, Department of Chemistry, Nanjing University, Nanjing 210093, P.R. China. Phone: 86-25-83593593; Fax: 86-25-83593593; E-mail: hxju{at}nju.edu.cn.

Purpose: To establish a quantitative system for evaluating the role of circulating tumor cells (CTC) in peripheral blood samples in patients who undergo surgery for treatment of esophageal cancer.

Experimental Design: One hundred fifty-five peripheral blood samples from 53 esophageal cancer patients were collected before surgery (B-1), immediately after surgery (B0), and on the 3rd day postoperatively (B+3). Eighty-nine samples from 22 benign patients who underwent thoracotomy and 30 healthy volunteers were obtained as controls. A real-time reverse transcription-PCR quantitative analysis system based on carcinoembryonic antigen (CEA) mRNA gene expression was designed for detection of CTC.

Results: This developed system can detect CEA mRNA-positive cells down to 3 cells per milliliter of peripheral blood. The cells in negative control groups were lower than the detection limit. The medians of 188 [95% confidence interval (95% CI), 155-498], 1513 (95% CI, 660-7,974) and 707 (95% CI, 737-3,005) CEA mRNA-positive cells per mL with the CEA-positive rates of 28.3%, 60.4%, and 42.9% in B-1, B0, and B+3 peripheral blood samples were obtained, respectively. There was statistically significant difference between B-1 and B0 (P = 0.0001) and between B-1 and B+3 (P = 0.0209). Fifty percent of patients with R > 0.4 showed metastasis in 1 year after surgery, whereas the probability was only 14.3% for patients with R < 0.4 (where R is CTC ratio of B+3 to B0, P = 0.043).

Conclusions: Esophageal cancer operation results in tumor cells dissemination and significant increase of CTC in peripheral blood, which is related to the developed metastasis. CTC are helpful for evaluating micrometastasis and have the potential for predicting recurrence in esophageal cancer.