J Clin Oncol. 2012 Feb 21. [Epub ahead of print]
Expression of Tumor-Derived Vascular Endothelial Growth Factor and Its Receptors Is Associated With Outcome in Early Squamous Cell Carcinoma of the Lung.
Pajares MJ, Agorreta J, Larrayoz M, Vesin A, Ezponda T, Zudaire I, Torre W, Lozano MD, Brambilla E, Brambilla C, Wistuba II, Behrens C, Timsit JF, Pio R, Field JK, Montuenga LM.
María J. Pajares, Jackeline Agorreta, Marta Larrayoz, Teresa Ezponda, Isabel Zudaire, Wenceslao Torre, María D. Lozano, Ruben Pio, and Luis M. Montuenga, Center for Applied Medical Research (CIMA) and Clinica Universidad de Navarra (CUN), University of Navarra, Pamplona, Spain; Aurélien Vesin, Elisabeth Brambilla, Christian Brambilla, and Jean-Francois Timsit, Institut Albert Bonniot, Centre Hospitalier Universitaire Albert Michallon, Institut National de la Santé et de la Recherche Médicale (INSERM) U823, and Université Joseph Fourrier, Grenoble, France; Ignacio I. Wistuba and Carmen Behrens, The University of Texas MD Anderson Cancer Center, Houston, TX; and John K. Field, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
PURPOSEAntiangiogenic therapies targeting the vascular endothelial growth factor (VEGF) pathway have yielded more modest clinical benefit to patients with non-small-cell lung cancer (NSCLC) than initially expected. Clinical data suggest a distinct biologic role of the VEGF pathway in the different histologic subtypes of lung cancer. To clarify the influence of histologic differentiation in the prognostic relevance of VEGF-mediated signaling in NSCLC, we performed a concomitant analysis of the expression of three key elements of the VEGF pathway in the earliest stages of the following two principal histologic subtypes: squamous cell carcinoma (SCC) and adenocarcinoma (ADC).
PATIENTS AND METHOD
We evaluated tumor cell expression of VEGF, VEGF receptor (VEGFR) 1, and VEGFR2 using automatic immunostaining in a series of 298 patients with early-stage NSCLC recruited as part of the multicenter European Early Lung Cancer Detection Group project. A score measuring the VEGF signaling pathway was calculated by adding the tumor cell expression value of VEGF and its two receptors. The results were validated in two additional independent cohorts of patients with NSCLC.
The combination of high VEGF, VEGFR1, and VEGFR2 protein expression was associated with lower risk of disease progression in early SCC (univariate analysis, P = .008; multivariate analysis, hazard ratio, 0.62; 95% CI, 0.42 to 0.92; P = .02). The results were validated in two independent patient cohorts, confirming the favorable prognostic value of high VEGF signaling score in early lung SCC.
Our results clearly indicate that the combination of high expression of the three key elements in the VEGF pathway is associated with a good prognosis in patients with early SCC but not in patients with ADC.