Offersen B V, Pfeiffer P, Hamilton-Dutoit S, Overgaard J
Danish Cancer Society, Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark.
Cancer. 2001 Apr 15;91(8):1500-9.
Tumor angiogenesis plays a pivotal role in tumor growth, maintenance, and metastasis. The objective of the current study was to evaluate the prognostic value of estimates of tumor angiogenesis and vascular endothelial growth factor (VEGF) status in 143 primary tumors from patients who underwent radical surgery for nonsmall-cell lung carcinoma (NSCLC).
Tumor sections were stained by immunohistochemistry for CD34 and VEGF. Angiogenesis was estimated both by a modification of the method described by Weidner and by the use of a 25-point Chalkley eyepiece graticule. VEGF intensity was evaluated semiquantitatively in three groups of patients. The vascular data were correlated with histopathologic tumor type and grade, TNM classification, patient age, and the endpoint (death).
The estimates of vascular score did not reveal any prognostic information. In 35 patients (24%), invasive tumor growth was identified with a highly ordered alveolar microvessel pattern. In parallel sections, the intensity of VEGF staining was weak in tumors that exhibited an alveolar microvessel pattern only, and it was more intense in tumors that demonstrated a mixed alveolar and diffuse angiogenic pattern. The 35 patients with alveolar microvessel pattern had a significantly better survival (P = 0.007). In a Cox multivariate analysis, the results demonstrated an independent bad prognostic value of high disease stage (P < 0.0001), adenocarcinoma (P = 0.004), greater age (P = 0.01), and angiogenic microvessel pattern (P = 0.01).
The authors believe that the alveolar vascular pattern represented preexisting alveolar vessels, that is, the alveoli were filled up by tumor cells that exploited the existing highly vascular bed of the lungs. Therefore, this subgroup was characterized by tumor progression without the induction of angiogenesis. The current data do not support a significant prognostic role for tumor angiogenesis in patients who are diagnosed with NSCLC. This may have implications for therapy aimed at inhibiting tumor growth by the inhibition of angiogenesis.
肿瘤血管生成在肿瘤生长、维持和转移中起关键作用。本研究的目的是评估肿瘤血管生成估计值和血管内皮生长因子（VEGF）状态对143例接受非小细胞肺癌（NSCLC）根治性手术患者的原发性肿瘤的预后价值。
肿瘤切片采用免疫组织化学法检测CD34和VEGF。通过对Weidner描述的方法进行改进以及使用25点Chalkley目镜测微计来估计血管生成。对三组患者的VEGF强度进行半定量评估。将血管数据与组织病理学肿瘤类型和分级、TNM分类、患者年龄及终点指标（死亡）进行关联分析。
血管评分估计未显示任何预后信息。在35例患者（24%）中，侵袭性肿瘤生长表现为高度有序的肺泡微血管模式。在平行切片中，仅表现为肺泡微血管模式的肿瘤中VEGF染色强度较弱，而表现为肺泡和弥漫性血管生成混合模式的肿瘤中VEGF染色强度更强。35例具有肺泡微血管模式的患者生存率明显更高（P = 0.007）。在Cox多因素分析中，结果显示疾病分期高（P < 0.0001）、腺癌（P = 0.004）、年龄较大（P = 0.01）和血管生成微血管模式（P = 0.01）具有独立的不良预后价值。
作者认为肺泡血管模式代表预先存在的肺泡血管，即肺泡被利用肺部现有高血管床的肿瘤细胞填充。因此，该亚组的特征是肿瘤进展而无血管生成诱导。目前的数据不支持肿瘤血管生成在NSCLC患者中具有显著的预后作用。这可能对旨在通过抑制血管生成来抑制肿瘤生长的治疗产生影响。
