The Study of Hepatocyte Growth Factor (HGF) in the Spreading of Colorectal Cancer -The Clinical Role of HGF in Dukes' Classification-

Tatsuto Ashizawa, Tatsuya Aoki^*, Tetsuo Sumi, Kenji Katsumata, Hidenori Tomioka, Yasuhisa Koyanagi^* and Keiichirou Yamamoto^**

Department of Digestive Tract Surgery, Hachioji Medical Center of Tokyo Medical University, ^*Department of Surgery, Tokyo Medical University, ^**Nishi Tokyo Central General Hospital

Purpose: HGF which has both mitogenic and motogenic activity in cancer cells, is involved in tumor invasion and metastasis. We evaluated serum HGF related to the spreading of colorectal cancer, and clarified the clinical role of HGF to classify Dukes' classification. Patients and Methods: In 53 patients (Dukes' A;7, B;15, C;17, D;14) with colorectal cancer, we assessed the correlation of HGF with 1) clinicopathological features (lymphatic invasion (ly), venous invasion (v), lymph node metastasis (n), hepatic metastasis (H)), 2) HGF-related factors (IL-6, IL-1β , TNF-α , TGF-β 1), 3) adhesion molecules (ELAM-1, ICAM-1, VCAM-1). And we evaluated these 8 factors (HGF, HGF-related factors, adhesion molecules) to classify 53 patients according to Dukes' classification. Results: 1) Significant relationships were seen between HGF and ly (p<0.05), n and H (p<0.01), 2) Significant relationships were seen between HGF and IL-6, TGF-β 1, ELAM-1 (p<0.01), and VCAM-1 (p<0.05), 3) HGF and IL-6 values in Dukes' D cases were significantly higher than those in Dukes' A, B, and C cases (p<0.01), 4) HGF, IL-6, and ELAM-1 were strongly related to distinguishing the Dukes' A/B group, Dukes' C group, and Dukes' D group. Conclusion: We suspect that HGF, which may be upregulated by IL-6 and TGF-β 1 from colorectal cancer cells, is involved in the invasive phase during the development of lymph node and hepatic metastasis. And HGF, ELAM-1, and IL-6 had particular diagnostic significance (sensitivity 67.7%, specificity 86.4%), which were the same values as tumor markers (CEA, CA19-9) and imaging diagnosis (US, CT), for Dukes' C and/or D group.

Key words
HGF, colorectal cancer, Lymph node metastasis, hepatic metastasis, Dukes' classification

Reprint requests
Tatsuto Ashizawa Department of Digestive Tract Surgery, Hachioji Medical Center of Tokyo Medical University 1163 Tate-machi, Hachioji-shi, 193-0998 JAPAN

Accepted
February 27, 2002

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