High serum YKL‐40 level after surgery for colorectal carcinoma is related to short survival

BACKGROUND YKL‐40 is a member of family 18 glycosyl hydrolases. YKL‐40 is a growth factor and may stimulate migration of endothelial cells. YKL‐40 may also play a role in inflammation and degradation of connective tissue. Elevated preoperative serum YKL‐40 levels in patients with colorectal carcinoma are associated with a significantly poorer prognosis compared to patients with normal serum YKL‐40. In the current study the authors evaluated the value of serum YKL‐40 in monitoring patients with colorectal carcinoma. METHODS YKL‐40 was determined by an in‐house radioimmunoassay method in serum obtained pre‐ and postoperatively from 324 patients who underwent curative resection (Dukes Stage A: 47; B: 148; C: 119; and D: 10). The patients were followed with serum YKL‐40 levels every 6 months postoperatively, and the median followup time was 82 months (range, 68–95). In that period 146 patients died. RESULTS Serum YKL‐40 was significantly decreased in the first postoperative blood sample in 62% of patients with high preoperative levels. In addition, patients with high serum YKL‐40 (adjusted for age) six months after curative operation had significantly shorter survival times (P = 0.0002) and shorter relapse free intervals (P = 0.004) than patients with normal postoperative serum YKL‐40. This result was independent of simultaneous serum carcinoembryonic antigen levels at six months. Analysis of survival by scoring serum YKL‐40 as a time‐dependent covariate in a Cox regression analysis showed that patients exhibiting elevated serum YKL‐40 had an increased hazard for death within the following six months compared to those patients with normal serum YKL‐40 level (hazard ratio [HR] = 9.6, 95% confidence interval [CI]: 6.0–15.5, P < 0.0001). Multivariate analysis including Dukes stage, age, gender, and tumor location as well as the time‐dependent serum YKL‐40 showed that high serum YKL‐40 was an independent prognostic variable of survival (HR = 8.5, 95% CI: 5.3–13.7, P < 0.0001). CONCLUSIONS These results suggest that determination of serum YKL‐40 during followup of patients operated on for colorectal carcinoma might be useful for monitoring curatively resected patients. Cancer 2002;95:267–74 © 2002 American Cancer Society. DOI 10.1002/cncr.10644 The growth factor YKL‐40 is a member of family 18 glycosyl hydrolases and is expressed by several types of cancer. It may play a role in inflammation and degradation of the connective tissue. Elevated preoperative levels of