1. ¹Department of Surgery, Medical Institute of Bioregulation, Kyushu University, 4546, Tsurumihara, Beppu 874-0838, Japan
2. ²Department of Surgical Oncology and Digestive Surgery, Field of Oncology, Course of Advanced Therapeutics, Kagoshima University, Graduate School of Medical and Dental Science, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima 890-8520, Japan
3. ³Gastric Surgery Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku 104-0045, Japan

Correspondence: Dr M Mori, E-mail: mmori@tsurumi.beppu.kyushu-u.ac.jp

Received 1 July 2008; Revised 11 November 2008; Accepted 11 November 2008; Published online 2 December 2008.

Abstract

Urokinase-type plasminogen activator receptor (uPAR) plays a central role in the plasminogen activation cascade and participates in extracellular matrix degradation, cell migration and invasion. We evaluated the expression level of uPAR mRNA and the presence of isolated tumour cells (ITCs) in bone marrow (BM) and peripheral blood (PB) in gastric cancer patients and clarified its clinical significance. We assessed specific uPAR mRNA expression by quantitative real-time reverse transcriptase- polymerase chain reaction (RT–PCR) in BM and PB in 846 gastric cancer patients as well as three epithelial cell markers, carcinoembryonic antigen (CEA), cytokeratin (CK)-19 and CK-7. The uPAR mRNA expression in bone marrow and peripheral blood expressed significantly higher than normal controls (P<0.0001). The uPAR mRNA in BM showed concordant expression with the depth of tumour invasion, distant metastasis, and the postoperative recurrence (P=0.015, 0.044 and 0.010, respectively); whereas in PB, we observed more intimate significant association between uPAR expression and clinicopathologic variables, such as depth of tumour invasion, the distant metastasis, the venous invasion and the clinical stage (P=0.009, 0.002, 0.039 and 0.008, respectively). In addition, the uPAR mRNA expression in PB was an independent prognostic factor for distant metastasis by multivariate analysis. We disclosed that it was possible to identify high-risk patients for distant metastasis by measuring uPAR mRNA especially in peripheral blood at the timing of operation in gastric cancer patients.