Hyodo I, Doi T, Endo H, Hosokawa Y, Nishikawa Y, Tanimizu M, Jinno K, Kotani Y
Department of Internal Medicine, National Shikoku Cancer Center Hospital, Matsuyama, Japan.
Eur J Cancer. 1998 Dec;34(13):2041-5. doi: 10.1016/s0959-8049(98)00282-2.
Circulating vascular endothelial growth factor (VEGF) was measured in gastric and colorectal cancer patients using an enzyme-linked immunosorbent assay (ELISA). Firstly, serum and plasma samples were collected from 20 normal controls to compare the values of VEGF and to determine which specimen type was most suitable for detecting circulating VEGF. Seventeen of 20 normal controls had plasma VEGF levels under the limit of detection (15 pg/ml) and the levels of the remaining three controls were 21, 22 and 38 pg/ml. In contrast, all serum samples indicated high levels of VEGF (mean 238 pg/ml), ranging from 44 to 450 pg/ml. In a time-course test of two normal controls serum VEGF values increased markedly between 30 and 60 min and remained high, whilst plasma VEGF values were low up to 480 min. Thus, plasma samples are more suitable for the measurement of circulating VEGF. Next, plasma VEGF levels were examined in 44 patients with gastric cancer (8 early, 7 advanced without remote metastasis and 29 metastatic), 13 with colorectal adenoma (2 with focal cancer) and 26 with colorectal carcinoma (8 advanced without metastasis and 18 metastatic) before treatment. An extremely high plasma concentration of VEGF was seen in some cancer patients with metastasis. To discriminate these patients, a cut-off level was determined, considering both the distribution of the sample concentration and the upper limit of 95% confidence area of VEGF in the cancer patients without metastasis. The cut-off value was 108 pg/ml and most cancer patients without metastases had VEGF levels below the cut-off value. In 11 of 29 metastatic gastric cancer patients (38%) and 9 of 18 metastatic colorectal cancer patients (50%), plasma VEGF levels were higher than the cut-off value. Survival was also analysed in the patients with metastasis. It was significantly longer in the patients with low VEGF levels (below the cut-off) than in those with high VEGF levels (logrank test, P = 0.042). 34 patients with metastasis (19 gastric cancer and 15 colorectal cancer) were treated with systemic chemotherapy, and their pretreatment levels of plasma VEGF and conventional tumour markers (CEA and CA19-9) were evaluated in relation to response. The response to chemotherapy was significantly higher in patients with low VEGF levels (< or = 108 pg/ml) than in those with high VEGF levels (P = 0.047). Such a difference was not observed with CEA/CA19-9. In conclusion, plasma VEGF is a useful marker for tumour metastasis and patient survival, and a possible predictive factor for the response of patients with gastrointestinal cancer to chemotherapy.
采用酶联免疫吸附测定（ELISA）法检测胃癌和结直肠癌患者循环血管内皮生长因子（VEGF）水平。首先，收集20名正常对照者的血清和血浆样本，比较VEGF值，以确定哪种样本类型最适合检测循环VEGF。20名正常对照者中有17人的血浆VEGF水平低于检测限（15 pg/ml），其余3名对照者的水平分别为21、22和38 pg/ml。相比之下，所有血清样本均显示VEGF水平较高（平均238 pg/ml），范围为44至450 pg/ml。在对两名正常对照者的时间进程测试中，血清VEGF值在30至60分钟之间显著升高并保持在高位，而血浆VEGF值在480分钟内一直较低。因此，血浆样本更适合用于测量循环VEGF。接下来，在44例胃癌患者（8例早期、7例无远处转移的进展期和29例转移期）、13例结直肠腺瘤患者（2例伴有局灶性癌）和26例结直肠癌患者（8例无转移的进展期和18例转移期）治疗前检测血浆VEGF水平。在一些有转移的癌症患者中观察到极高的血浆VEGF浓度。为了区分这些患者，综合考虑样本浓度分布和无转移癌症患者VEGF的95%置信区间上限来确定临界值。临界值为108 pg/ml，大多数无转移的癌症患者VEGF水平低于临界值。29例转移性胃癌患者中有11例（38%）和18例转移性结直肠癌患者中有9例（50%）的血浆VEGF水平高于临界值。还对有转移的患者进行了生存分析。VEGF水平低（低于临界值）的患者的生存期明显长于VEGF水平高的患者（对数秩检验，P = 0.042）。34例有转移的患者（19例胃癌和15例结直肠癌）接受了全身化疗，并评估了他们治疗前的血浆VEGF水平和传统肿瘤标志物（CEA和CA19-9）与疗效的关系。VEGF水平低（≤108 pg/ml）的患者对化疗的反应明显高于VEGF水平高的患者（P = 0.047）。CEA/CA19-9未观察到这种差异。总之，血浆VEGF是肿瘤转移和患者生存的有用标志物，也是胃肠道癌患者化疗反应的可能预测因素。
