Patterns of angiogenesis in nonsmall-cell lung carcinoma

Abstract

BACKGROUND 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). METHODS 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). RESULTS 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). CONCLUSIONS 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. Cancer 2001;91:1500–9. © 2001 American Cancer Society.

Association of macrophages, mast cells and eosinophil leukocytes with angiogenesis and tumor stage in non-small cell lung carcinomas (NSCLC)

“…On the other hand, angiogenesis does not appear to have a major impact on the biological behavior of NSCLCs. While some studies suggested that angiogenesis might be an independent prognostic factor, several major studies failed to show any relation between tumor vascularisation and survival [3][4][5][6][7]. In this study, although NVES was found to be higher in early stage group, VSD value was not related to stage.…”

“…Tumor vascularisation in NSCLCs has been described to be composed of either newly formed vessels or preexisting vessels in the alveolar septae or a combination of both. An alveolar vascular growth pattern, in which tumor cells fill the alveolar spaces, entrapping, but not destroying the alveolar septa with co-opted vessels has been believed to represent preexisting alveolar vessels [5,30]. In this study, none of the cases had a pure alveolar growth pattern.…”

“…One of the first studies of the effect of tumor angiogenesis on biologic behavior of non-small cell lung carcinomas (NSCLCs) was reported by Macchiarini et al [3]. Subsequently, a number of studies on this subject have been published with conflicting results [4][5][6][7].…”

Angiogenesis in non-small cell lung cancer: The prognostic impact of neoangiogenesis and the cytokines VEGF and bFGF in tumours and blood

“…Several studies have shown that the presence of neoangiogenesis is a significantly negative prognostic factor for both overall and disease-free survival in lung cancer [17][18][19][20][21][22][23][24].…”

Prognostic significance of vessel architecture and vascular stability in non-small cell lung cancer

“…Interestingly, besides tumours displaying an ''angiogenic'' disorganized microvascular pattern as evidence of angiogenesis induction we further found a distinct ''alveolar'' vascular pattern in a major subset of the investigated samples which looked similar to the normal alveolar structure of the lung. A similar pattern has been previously addressed as evidence of coopting the preexisting vasculature [6,26]. In fact, the normal lung provides two vasculature systems deriving from the pulmonary and the bronchial arteries that both may be adopted by a growing tumour without the development of hypoxic areas and the subsequent need for angiogenesis induction [27].…”