No abstract

YKL-40 is a growth factor for connective tissue cells and stimulates migration of endothelial cells. YKL-40 is secreted by cancer cells, and elevated serum YKL-40 in patients with metastatic breast cancer and colorectal cancer is associated with a poorer prognosis as compared to patients with normal serum YKL-40. In the present study we evaluated the associations of preoperative serum YKL-40 in 271 patients with primary breast cancer in relation to relapse-free survival and overall survival. The median follow-up time was 5.9 years. There were 77 relapses and 69 patients died. The median serum YKL-40 concentration in the patients was 57 microg/l (range 22-688 microg/l) and significantly elevated (p < 0.0001) compared to serum YKL-40 in healthy females. Nineteen percent of the patients had high serum YKL-40 (i.e., >95 percentile of healthy females). Patients with high serum YKL-40 had shorter relapse-free interval (hazard ratio (HR) = 1.77, 95% confidence interval (CI): 1.06-2.95, p = 0.028) and overall survival (HR = 1.78, 95% CI: 1.04-3.05, p = 0.036) than patients with normal serum YKL-40. Serum YKL-40 was higher (p = 0.005) in lymph node positive patients as compared to lymph node negative patients. Multivariate analysis including lymph node status, estrogen receptor status, tumor size, age, menstrual status and serum YKL-40 showed that serum YKL-40 was an independent prognostic variable of relapse-free survival (HR = 1.73, 95% CI: 1.03-2.91, p = 0.039). Our results show that serum YKL-40 in patients with primary breast cancer at time of operation is only elevated in a small group of patients, but these patients have a shorter recurrence free interval. Further studies are required to determine the biological function of YKL-40 in breast cancer.

Our results show that although bFGF is elevated in breast carcinomas compared to normal breast tissue it is not related to microvessel density and it is not an independent predictor of survival in breast cancer patients. Basic FGF may be one of multiple factors that synergise with other growth factors such as VEGF to enhance angiogenesis.

Angiogenesis is essential for tumor growth and metastases. Studies in breast carcinomas suggest that microvessel quantitation as a measure of angiogenesis might be one of the most powerful prognostic tools available. Node negative breast cancer is a particular group for which better prognostic markers would be helpful. We therefore measured microvessel density in a series of well characterised node negative breast carcinomas to evaluate angiogenesis as a prognostic marker and assess its relationship to epidermal growth factor receptor (EGFR) and estrogen receptor (ER), which have previously been reported to be of value. 109 patients with a mean age of 55 years and a median follow-up of 25 months were examined. Vessels were immunohistochemically highlighted using an antibody to platelet endothelial cell adhesion molecule CD31, and microvessel density was quantified using a Chalkley point eyepiece graticule. No significant correlation was observed with patient age, tumor size, grade, ER, or EGFR expression. In a univariate analysis of survival, whereas ER expression was not a significant indicator of either relapse-free (RFS) or overall survival (OS), vascular count (VC) predicted both early RFS and OS (p = 0.01) and p = 0.028 respectively). Furthermore, in patients with ER positive tumors, a subgroup usually considered to have a good prognosis, there was a significant reduction in RFS and OS if tumors had high VCs (p = 0.05 and p = 0.002 respectively). A further statistically significant reduction in RFS (p = 0.05) was observed for EGFR positive highly vascular tumors.(ABSTRACT TRUNCATED AT 250 WORDS)