The Study of IL-6 in the Spread of Colorectal Cancer -The Role of IL-6 as a Prognostic Factor-

Tatsuto Ashizawa, Tetsuo Sumi, Makoto Takagi, Tatsuyuki Yamazaki, Toshiaki Aoki, Hidenori Tomioka, Syouji Maruyama¹⁾, Masafumi Takimoto²⁾, Tatsuya Aoki³⁾ and Yasuhisa Koyanagi³⁾

Department of Digestive Tract Surgery, Hachioji Medical Center of Tokyo Medical University
¹⁾Department of Surgery and ²⁾Department of Pathology, Tokyo Metropolitan Toshima Hospital
³⁾Department of Surgery, Tokyo Medical University

Purpose: We studied the relationship between serum interleukin-6 (IL-6) and lymph node and hepatic metastasis from colorectal cancer, clarifying the role of IL-6 as a prognostic factor. Patients and Methods: In 65 patients with colorectal cancer and 20 healthy volunteers, we statistically assessed the correlation of preoperative IL-6 value (pg/ml) with 1) Dukes'classification, 2) lymph node metastasis (n), 3) hepatic metastasis (H'), 4) IL-6-related factors (HGF, IL-1β, TNF-α, TGF-β1), 5) adhesion molecules (ICAM-1, VCAM-1, E-selectin). 6) Supposing that cutoff value of IL-6 was set at 5.81 (mean+2SD for 25 Dukes'A and B patients), we determined the association between IL-6 elevation and prognosis regarding to stage III, IV and all patients. 7) We also examined the expression of IL-6 in tumor tissue. Results: 1) IL-6 in Dukes'C and D cases (7.12, 18.57) was significantly higher than in control cases (1.05)(p<0.01). 2) A significant relationship was seen between IL-6 and lymph node metastasis. IL-6 in n2 (+) and n3 (+) cases (10.20, 14.23) was significantly higher than in n (-) cases (3.27)(p<0.01). And IL-6 in H'(+) cases (18.57) was significantly higher than in H₀' (4.93), showing a significant relationship between IL-6 and hepatic metastasis (p<0.01). 3) A significant relationship was seen between IL-6 and HGF (p<0.01), ICAM-1 (p<0.01), VCAM-1 (p<0.01) and E-selectin (p<0.01). 4) When the cutoff value of IL-6 was set at 5.81, overall cumulative survival for 43 patients with IL-6 exceeding 5.81 was significantly lower than for 20 patients with IL-6 of 5.81 or less (p<0.01). The significant relationship remained among patients in stage III and IV. 5) In all cases with high serum level (more than 25.0 pg/ml) of IL-6, immunohistochemical staining showed positive findings for IL-6 in the cytoplasm of cancer cell. Conclusion: We suspect that IL-6, which may be released from colorectal cancer cells, is involved in the invasive phase during the development of lymph node and/or hepatic metastasis. Our results indicate that serum IL-6 could be used as a prognostic factor in colorectal cancer patients.

Key words
IL-6, colorectal cancer, lymph node metastasis, hepatic metastasis, prognostic factor

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

Accepted
January 28, 2004

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