Vascular endothelial growth factor and soft tissue sarcomas: Tumor expression correlates with grade
Vascular endothelial growth factor and soft tissue sarcomas: Tumor expression correlates with grade
复制标题
DOI：
10.1007/s10434-001-0260-9
复制
发表时间：
2001-04-01
影响因子：
3.7
通讯作者：
Eisenberg, B
中科院分区：
文献类型：
--
作者：
Chao, C;Al-Saleem, T;Eisenberg, B
血管内皮生长因子（VEGF）是一种在各种上皮恶性肿瘤中过表达的内皮特异性丝裂原，被认为是血管生成的有效调节剂。我们假设一些软组织肉瘤，由于其血液转移的高倾向(1)会过度表达VEGF，(2)表达程度可能是疾病特异性生存的重要生物学预测指标，(3)与原发肿瘤相比，复发肿瘤会表达更高或更高的VEGF。方法：选取1989 ~ 1995年79例软组织肉瘤手术标本石蜡包埋组织，采用兔多克隆抗vegf抗体（浓度为2 mug/ml）进行染色。两名对临床病理数据不知情的研究人员评估了载玻片中VEGF的高或低表达。12例患者原发肿瘤有VEGF表达，并与复发肿瘤进行比较。fisher精确试验评估了VEGF表达的差异；根据Kaplan和Meier方法进行生存分析。结果：78%（29 / 37）死于疾病的患者有高VEGF表达。然而，VEGF表达并不是总生存率或无病生存率的独立预测因子。肿瘤分级与VEGF表达显著相关。对于低级别肿瘤，13例中有7例表达低VEGF，而对于高级别肿瘤，66例中有53例表达高VEGF （P = 0.016）。12个配对肿瘤样本中有7个表达相同的VEGF免疫染色。结论：本研究中大多数高级别软组织肉瘤具有高强度的VEGF表达。这一发现可能为个体软组织肉瘤提供有用的信息，并为高风险患者使用抗血管生成策略的治疗和生物靶向提供基础。然而，在我们的分析中，在考虑肿瘤分级后，VEGF似乎并不是临床结果的独立预测因子。
Introduction: Vascular endothelial growth factor (VEGF), an endothelial-specific mitogen overexpressed in various epithelial malignancies is thought to be a potent regulator of angiogenesis. We hypothesized that some soft tissue sarcomas, due to their high propensity for hematogenous metastases (1) would overexpress VEGF, (2) that the degree of expression may represent a significant biologic predictor for disease-specific survival, and (3) that recurrent tumor would express as high or higher VEGF compared with the primary tumor.Methods: Selected paraffin-embedded tissue of surgical specimens from 79 patients with soft tissue sarcomas, treated between 1989 and 1995 were stained with a rabbit polyclonal anti-VEGF antibody at a concentration of 2 mug/ml. Slides were assessed for VEGF expression os high or low by two investigators blinded to the clinicopathologic data. Twelve patients had VEGF expression of their primary tumors, and their recurrent tumors were compared. The Fishers' exact test assessed fur differences in VEGF expression; survival analyses were performed according to the methods of Kaplan and Meier.Results: Seventy-eight percent (29 of 37) of patients who died of disease had high VEGF expression. However, VEGF expression was not an independent predictor of either overall or disease-free survival. Tumor grade correlated with VEGF expression significantly. For the low-grade tumors, 7 of 13 expressed low VEGF, whereas for high-grade tumors, 53 of 66 expressed high VEGF (P = .016). Seven of the 12 paired tumor samples expressed identical VEGF immunostaining.Conclusions: The majority of high-grade soft tissue sarcomas in this study have high intensity VEGF expression. This finding may provide useful information on individual soft tissue sarcomas and offer the basis for therapeutic and biologic targeting in high-risk patients using anti-angiogenesis strategies. However, in our analysis, after accounting for tumor grade, VEGF does not seem to be an independent predictor of clinical outcome.