Clinical Significance of Circulating Cancer Cells in Peripheral Blood Detected by Reverse Transcriptase-Polymerase Chain Reaction in Patients with Breast Cancer

Clinical Significance of Circulating Cancer Cells in Peripheral Blood Detected by Reverse Transcriptase-Polymerase Chain Reaction in Patients with Breast Cancer

XIAO-YONG AN, HIROSHI EGAMI, NAOKO HAYASHI, YUJI KURUSU, JUN-ICHI YAMASHITA and MICHIO OGAWA

The Second Department of Surgery, Kumamoto University Medical School Kumamoto 860-8556

Detection of breast cancer micrometastases based on specific genetic markers may provide useful information to justify appropriate therapeutic strategies. We examined the presence of a carcinoembryonic antigen (CEA) messenger RNA(mRNA) in the peripheral blood of 32 patients with varying stages of breast cancers by means of the reverse transcriptase-polymerase chain reaction (RT-PCR) assay prior to and after the curative operation. CEA mRNA were detected in the peripheral blood samples from 12 (38%) out of 32 breast cancer patients prior to surgery. Among 12 CEA mRNA-positive patients prior to surgery, 4 (33.3%) relapsed from breast cancer within 2 years after surgery. Moreover, CEA mRNA was detected in the peripheral blood samples obtained prior to surgery in 3 out of 11 patients (27.2%) with a stage I disease. One out of three of these patients had a relapse in lung. There were four patterns of CEA mRNA expression, (+, +), (+, –), (–, +), and (–, –) in the pre- and post-operative blood samples. In 12 CEA mRNA-positive patients submitted to surgical resection of the primary tumor, persistence of CEA mRNA expression was observed in five patients (+, +) within a month after surgical treatment. Three out of these 5 patients (60%) relapsed from breast cancer within 2 years after surgery. In 7 other patients (+, –), CEA mRNA expression was not detected within a month after tumor removal, and recurrence occurred in 1 out of the 7 patients (14%) within 2 years after surgery. In 19 patients, CEA mRNA expression was not detected in pre- or post-operative blood samples (–, –). There was a patient whose blood sample was negative for CEA mRNA before the operation, but changed to show a positive result after surgery (–, +). No recurrence was found in 20 of CEA mRNA-negative patients prior to surgery (–, +), (–, –). This study suggested that the presence of CEA mRNA expression in preoperative peripheral blood sample represent the progression of the disease, especially the risk of hematogenous metastasis in the patients in spite of their clinical stage, and the presence of CEA mRNA in the postoperative blood sample may represent the evidence of a residual disease. Thus consideration might be given for adding combined multi-modal therapy.

Keywords —— CEA mRNA; RT-PCR; peripheral blood; breast cancer

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Tohoku J. Exp. Med., 2001, 193, 153-162

Address for reprints: Michio Ogawa, M.D., Ph.D., The Second Department of Surgery, Kumamoto University Medical School, 1-1-1 Honjo, Kumamoto 860-8556, Japan.

e-mail: mogawa@kaiju.medic.kumamoto-u.ac.jp