Prognostic impact of matched preoperative plasma and serum VEGF in patients with primary colorectal carcinoma

Abstract

In serum, the major part of vascular endothelial growth factor derives from in vitro degranulation of granulocytes and platelets. Therefore, plasma may be preferred for vascular endothelial growth factor measurements. However, which specimen is the best predictor of survival is still debated. The present study analyzed the prognostic value of matched preoperative serum and plasma vascular endothelial growth factor concentrations in patients with colorectal cancer. To establish the reference range among healthy people, vascular endothelial growth factor was analyzed in 50 matched EDTA-plasma and serum samples from healthy blood donors. Preoperatively, in 524 patients with colorectal cancer, matched plasma and serum vascular endothelial growth factor concentrations were analyzed. In the colorectal cancer patients, the median plasma vascular endothelial growth factor concentration (44 pg ml 71 ) was significantly (P=0.01) higher than the median plasma vascular endothelial growth factor concentration (30 pg ml 71 ) in the healthy blood donors. In serum, no significant (P=0.30) difference in the median vascular endothelial growth factor concentration was found between colorectal cancer patients (268 pg ml 71 ) and healthy blood donors (220 pg ml 71 ). The preoperative vascular endothelial growth factor concentrations were dichotomized by the 95th percentile of the healthy blood donors (plasma=112 pg ml 71 , serum=533 pg ml 71 ). In univariate survival analyses, both high plasma vascular endothelial growth factor (4112 pg ml 71 ) and high serum vascular endothelial growth factor (4533 pg ml 71 ) predicted a reduced survival. In multivariate survival analyses, high serum vascular endothelial growth factor (4533 pg ml 71 ) independently predicted a reduced survival (HR=1.65, P=0.015), while high plasma vascular endothelial growth factor (4112 pg ml 71 ) did not (HR=1.27, P=0.23). This study indicates that preoperative serum vascular endothelial growth factor apparently is a better predictor of overall survival than the preoperative plasma vascular endothelial growth factor. Keywords: angiogenesis; colorectal cancer; prognosis; VEGF Vascular endothelial growth factor (VEGF) is one of the strongest promoters of angiogenesis, and it has been indicated, that the preoperative serum VEGF concentration is a prognostic marker in a variety of solid tumours (Salven et al, 1999a;Chin et al, 2000). In a previous study including 614 patients, it was shown that pre-operative serum VEGF concentration, independent of Dukes stage, was a strong predictor of overall survival of patients with colorectal cancer (CRC) (Werther et al, 2000). However, VEGF is stored in circulating white blood cells and platelets (Nielsen et al, 1999;Salven et al, 1999b) and several reports have indicated, that elevated VEGF concentrations in serum may be a reflection of degranulation of platelets and white blood cells during in vitro clotting, rather than a reflection of an ongoing angiogenic activity in the tumour (Webb et al, 1998). In plasma, white cell and...

Prognostic value of serum levels of interleukin 6 and of serum and plasma levels of vascular endothelial growth factor in hormone-refractory metastatic breast cancer patients

“…As most serum VEGF is released from platelets during blood clotting, it has been suggested that plasma VEGF may be a better reflection of ongoing angiogenic activity, although this assumption has been challenged (Banks et al, 1998;Salven et al, 1999a;Wynendaele et al, 1999;George et al, 2000). To date, plasma VEGF has not been shown to be a better prognostic factor than serum VEGF in any solid tumour (Werther et al, 2002).…”

The influence of fractionated radiation therapy on plasma vascular endothelial growth factor (VEGF) concentration in dogs with spontaneous tumors and its impact on outcome

“…Correspondingly, palliatively treated dogs (group B) with a low plasma VEGF level that responded to therapy had also a significantly longer TTF and a longer live span. In a human colorectal cancer study, it was also shown that high plasma and serum VEGF concentration prior to surgery predicted decreased overall survival [5,29].…”

“…When serum and plasma VEGF in patients with primary colorectal carcinoma were analyzed separately, both, high serum and high plasma VEGF concentrations predicted for shorter survival, but significance was only reached for serum VEGF values [29]. In contrast, high plasma VEGF was shown to be a significant predictor of reduced overall survival and of earlier onset of local recurrence for patients with breast cancer [23,30].…”

“…Low pre-operative serum VEGF levels (!575 pg/ml) were shown to correlate with increased disease free survival, in human patients with colorectal cancer indicating that serum VEGF was a good predictor for outcome [29]. When serum and plasma VEGF in patients with primary colorectal carcinoma were analyzed separately, both, high serum and high plasma VEGF concentrations predicted for shorter survival, but significance was only reached for serum VEGF values [29].…”

A consistent shift in VEGF determinations between two different ELISA batch numbers

“…In February 2002, we published an article in the Br J Cancer concerning the prognostic impact of matched preoperative plasma and serum VEGF in patients with primary colorectal carcinoma (Werther et al, 2002).…”