Patterns of angiogenesis in nonsmall-cell lung carcinoma.
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.
Offersen
B V
BV
Danish Cancer Society, Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark. bvo@oncology.dk
Pfeiffer
P
P
Hamilton-Dutoit
S
S
Overgaard
J
J
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply* / Q000737:chemistry / Q000473:pathology; D018450:Disease Progression; D016228:Endothelial Growth Factors / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000098:blood supply* / Q000737:chemistry / Q000473:pathology; D008222:Lymphokines / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D011379:Prognosis; D011650:Pulmonary Alveoli / Q000473:pathology; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D014408:Biomarkers, Tumor; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors