Linderholm B, Tavelin B, Grankvist K, Henriksson R
Department of Oncology, Umeå University Hospital, Sweden.
J Clin Oncol. 1998 Sep;16(9):3121-8. doi: 10.1200/JCO.1998.16.9.3121.
The prognostic value of vascular endothelial growth factor (VEGF) protein, known to stimulate endothelial growth and angiogenesis, was evaluated in node-negative breast carcinoma (NNBC) and compared with established prognostic factors.
In 525 consecutive patients with primary invasive NNBC (T1-2N0M0; tumor, node, metastasis stage), of whom 500 patients did not receive any systemic therapy, the cytosolic levels of VEGF165 were measured by using a quantitative enzyme-linked immunosorbent assay. The median follow-up was 46 months. Univariate and multivariate analyses were performed.
VEGF level was significantly inversely correlated with estrogen receptor (ER) positivity but positively associated with tumor size and histologic grade. Patients with VEGF levels above the median value (2.40 pg/microg of DNA) showed a significantly shorter survival time (P=.0012) than patients with levels less than the median value, also when analyzed as a continuous variable (P=.0277). Tumor size, grade, and ER expression were all statistically significant for overall survival in univariate analyses (P=.0069, P=.014, and P < .001, respectively). Multivariate analysis showed that VEGF level was the strongest predictor of overall survival (P=.0199). Histologic grade was also an independent predictor of survival (P=.0477). Among the 381 patients with ER-positive tumors, a group in general considered to have a good prognosis, we found a significant reduction in survival for those with levels of VEGF greater than the median value (P=.0009).
The results suggest that the level of VEGF165 protein is an independent, strong prognostic factor for survival in patients with NNBC, especially in the subgroup of patients with ER positivity. Thus, cytosolic VEGF165 might be useful to select patients for adjuvant systemic therapy.
评估血管内皮生长因子(VEGF)蛋白(已知可刺激内皮生长和血管生成)在淋巴结阴性乳腺癌(NNBC)中的预后价值,并与已确立的预后因素进行比较。
在525例连续性原发性浸润性NNBC患者(T1 - 2N0M0;肿瘤、淋巴结、转移分期)中,500例患者未接受任何全身治疗,采用定量酶联免疫吸附测定法测量VEGF165的胞浆水平。中位随访时间为46个月。进行了单因素和多因素分析。
VEGF水平与雌激素受体(ER)阳性呈显著负相关,但与肿瘤大小和组织学分级呈正相关。VEGF水平高于中位数(2.40 pg/μg DNA)的患者生存时间显著短于VEGF水平低于中位数的患者(P = 0.0012),将VEGF水平作为连续变量分析时也是如此(P = 0.0277)。在单因素分析中,肿瘤大小、分级和ER表达对总生存均具有统计学意义(分别为P = 0.0069、P = 0.014和P < 0.001)。多因素分析显示,VEGF水平是总生存的最强预测因素(P = 0.0199)。组织学分级也是生存的独立预测因素(P = 0.0477)。在381例ER阳性肿瘤患者(通常被认为预后良好的一组)中,我们发现VEGF水平高于中位数的患者生存显著降低(P = 0.0009)。
结果表明,VEGF165蛋白水平是NNBC患者生存的独立、强预后因素,尤其是在ER阳性患者亚组中。因此,胞浆VEGF165可能有助于选择辅助全身治疗的患者。