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Combination of low vascular endothelial growth factor A (VEGF‐A)/VEGF receptor 2 expression and high lymphocyte infiltration is a strong and independent favorable prognostic factor in patients with nonsmall cell lung cancer
Author(s) -
Donnem Tom,
AlShibli Khalid,
Andersen Sigve,
AlSaad Samer,
Busund LillTove,
Bremnes Roy M.
Publication year - 2010
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.25333
Subject(s) - medicine , vascular endothelial growth factor , lung cancer , angiogenesis , cd8 , tissue microarray , oncology , cancer research , immunohistochemistry , hazard ratio , immune system , pathology , immunology , vegf receptors , confidence interval
BACKGROUND: There seems to be a close interplay between angiogenesis and the immune system. The authors of this report investigated the prognostic role of angiogenic markers in coexpression with immune system markers in patients with nonsmall cell lung cancer (NSCLC). METHODS: Tumor resection samples from 335 patients with stage I to IIIA NSCLC were obtained, and tissue microarrays were constructed. Immunohistochemistry was used to evaluate the expression of vascular endothelial growth factor (VEGF) A (VEGF‐A), VEGF receptor 2 (VEGFR‐2), and lymphocytes that were positive for the cluster of differentiation 4 (CD4) and CD8 coreceptors. RESULTS: In univariate analysis, 5‐year survival rates were 87% for the combination of low tumor cell expression of VEGF‐A and VEGFR‐2 (↓VEGF‐A/↓VEGFR‐2) and high tumor cell expression of CD4 and CD8 (↑CD4/↑CD8) (n = 19), 58% for mixed combinations (n = 290), and 27% for the ↑VEGF‐A/↑VEGFR‐2 and ↓CD4/↓CD8 combination (n = 26). In multivariate analysis, the coexpression of ↑VEGF‐A/↑VEGFR‐2 and ↓CD4/↓CD8 was an independent negative prognostic factor (hazard ratio, 9.16; 95% confidence interval, 2.11‐39.8; P = .003). CONCLUSIONS: Low tumor cell VEGF‐A and VEGFR‐2 expression in combination with high adaptive immune cell expression in the tumor‐related stroma had a strong and independent favorable prognostic impact in patients with NSCLC. Cancer 2010. © 2010 American Cancer Society.