Prognostic impact of VEGF, CD31, CD34, and CD105 expression and tumour vessel invasion after radical surgery for IB–IIA non-small cell lung cancer

• Published in: Journal of clinical pathology Vol. 57; no. 6; pp. 591 - 597
• Main Authors: Mineo, T C, Ambrogi, V, Baldi, A, Rabitti, C, Bollero, P, Vincenzi, B, Tonini, G
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and Association of Clinical Pathologists 01.06.2004; BMJ; BMJ Publishing Group LTD; Copyright 2004 Journal of Clinical Pathology
• Subjects: Adult; Aged; Angiogenesis Inducing Agents - metabolism; Antigens, CD34 - metabolism; Biological and medical sciences; Biomarkers, Tumor - metabolism; Carcinoma, Non-Small-Cell Lung - blood supply; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - surgery; confidence interval; Epidemiologic Methods; Female; Humans; Investigative techniques, diagnostic techniques (general aspects); Lung Neoplasms - blood supply; Lung Neoplasms - metabolism; Lung Neoplasms - surgery; Male; Medical sciences; microvessel density; Middle Aged; MVD; neoangiogenesis; Neoplasm Proteins - metabolism; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - pathology; non-small cell lung cancer; NSCLC; odds ratio; Original; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Platelet Endothelial Cell Adhesion Molecule-1 - metabolism; Pneumology; Pneumonectomy; Postoperative Period; Prognosis; TBS; thoracic surgery; Treatment Outcome; trisphosphate buffered saline; Tumors of the respiratory system and mediastinum; vascular endothelial growth factor; Vascular Endothelial Growth Factors - metabolism; VEGF; Lung disease; Prognosis; Respiratory disease; Lung cancer; Malignant tumor; non-small cell lung carcinoma; Radical; Invasion; Anatomic pathology; Vascular endothelium growth factor; Treatment; Surgery; Platelet endothelial cell adhesion molecule 1; Bronchus disease
• ISSN: 0021-9746; 1472-4146
• DOI: 10.1136/jcp.2003.013508

Aims: To evaluate the prognostic impact of tumour angiogenesis assessed by vascular endothelial growth factor (VEGF), microvessel density (MVD), and tumour vessel invasion in patients who had undergone radical resection for stage IB–IIA non-small cell lung cancer (NSCLC). Methods: Fifty one patients (42 men, nine women; mean age, 62.3 years; SD, 6.9) undergoing complete surgical resection (35 lobectomy, 16 pneumonectomy) of pathological stage IB (n  =  43) and IIA (n  =  8) NSCLC were evaluated retrospectively. No patient underwent postoperative chemotherapy or neoadjuvant treatment. Tumour specimens were stained for VEGF and specific MVD markers: CD31, CD34, and CD105. Results: VEGF expression significantly correlated with high CD105 expression (p < 0.0001) and tumour vessel invasion (p  =  0.04). Univariate analysis showed that those patients with VEGF overexpression (p  =  0.0029), high MVD by CD34 (p  =  0.0081), high MVD by CD105 (p  =  0.0261), and tumour vessel invasion (p  =  0.0245) have a shorter overall survival. Furthermore, multivariate Cox regression analysis showed that MVD by CD34 (p  =  0.007), tumour vessel invasion (p  =  0.024), and VEGF expression (p  =  0.042) were significant predictive factors for overall survival. Finally, the presence of both risk factors, tumour vessel invasion and MVD by CD34, was highly predictive of poor outcome (odds ratio, 3.4; 95% confidence interval, 1.7 to 6.5; p  =  0.0002). Conclusions: High MVD by CD34 and tumour vessel invasion are more closely related to poor survival than the other neoangiogenetic factors in stage IB–IIA NSCLC. This may be because these factors are more closely related to the metastatic process.