We aim to determine the clinical usefulness of pre-operative serum vascular endothelial growth factor (VEGF) as a predictor of outcome in patients undergoing curative resection for colorectal cancer. Serum VEGF was assayed by quantitative ELISA in 81 patients prior to curative resection for node-negative (n = 53) and node-positive (n = 28) disease. Median follow-up for patients without cancer death was 27 months (range 21–37). Pre-operative serum VEGF was significantly higher in patients who went on to develop metastases than those who did not (median, 713 pg ml–1 vs. 314 pg ml–1, P < 0.0001). Using multivariate Cox regression analysis, pre-operative serum VEGF was the most important prognostic factor independent of nodal status and adjuvant chemotherapy, and was superior to nodal status in predicting outcome (P < 0.00001). At 575 pg ml–1, pre-operative serum VEGF was 64% sensitive and 89% specific in predicting the development of metastases in curative resections, with a positive predictive value of 73% and a negative predictive value of 85%. Pre-operative serum VEGF is a powerful predictor of outcome following curative surgery for colorectal cancer. These data support the measurement of pre-operative serum VEGF as a method for selecting patients who require adjuvant therapy. © 2000 Cancer Research Campaign http://www.bjcancer.com

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Summary Timing of surgery in premenopausal patients with breast cancer remains controversial. Angiogenesis is essential for tumour growth and vascular endothelial growth factor (VEGF) is one of the most potent angiogenic cytokines. We aimed to determine whether the study of VEGF in relation to the menstrual cycle could help further the understanding of this issue of surgical intervention. Fourteen premenopausal women were recruited, along with three post-menopausal women, a woman on an oral contraceptive pill and a single male subject. Between eight and 11 samples were taken per person, over one menstrual cycle (over 1 month in the five controls) and analysed for sex hormones and VEGF165. Serum VEGF was significantly lower in the luteal phase and showed a significant negative correlation with progesterone in all 14 premenopausal women. No inter-sample variations of VEGF were noted in the controls. Serum from both phases of the cycle from one subject was added to MCF-7 breast cancer cells; VEGF expression in the supematant was lower in the cells to which the luteal phase serum was added. The lowering of a potent angiogenic cytokine in the luteal phase suggests a possible decreased potential for micrometastasis establishment in that phase. This fall in VEGF may be an effect of progesterone and should be the focus of future studies.Keywords: VEGF; breast cancer, oestradiol; progesterone; timing of surgery TIhe controversy of the timing of surgical intervention in premenopausal breast cancer patients was initiated when Hrushesky et al (1989). in a study of 44 patients. observed a better survival for tumours resected between days 7 and 20 of the menstrual cycle.Various studies follox%ed. with differing results. though four major studies have favoured the second half of the cycle. when the influence of progesterone predominates (Badwe et al. 1991;Senie et al. 1991: Veronesi et al. 1994: Goldhirsch et al. 1997.Angiogenesis has been shown to be essential for both the growth and metastasis of many solid tumours. with a large number of the data resulting from studies of breast cancer. In the absence of angiogenesis. a tumour will not grow beyond the size of 2-3 mm (Gimbrone et al. 1972 MATERIALS AND METHODSFourteen premenopausal women were recruited with no prior history of any breast disorders. None had any significant medical history. except one woman, who had ankylosing spondylosis.Three groups of controls were included: three post-menopausal women. one premenopausal woman on a low-dose oestrogen combined oral contraceptive pill and one male subject. Informed verbal consent was obtained from all subjects.Blood samples were taken at 4-day intervals in both the subjects and the controls. In the case of the premenopausal women, these were taken from day 1 of one menstrual cycle through to day 1 of the following cycle (8-11 samples per person). Two extra periovulatory samples were taken in four premenopausal women: thus. a total of 123 samples were taken from the premenopausal women. 65 in the follicular phase and 58 in t...

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