Association between EGFR/KRAS mutation and expression of VEGFA, VEGFR and VEGFR2 in lung adenocarcinoma.

Epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (KRAS) are two of the most notable driver genes in lung cancer, whilst vascular endothelial growth factor (VEGF) signaling serves a critical function in tumor angiogenesis. However, few studies have focused on the potential connection between EGFR/KRAS mutational status, and VEGFA, VEGF receptor (VEGFR)1 and VEGFR2 expression in lung adenocarcinoma. EGFR (exon 19, 20 and 21) and KRAS (exon 2) mutations were detected using an amplification refractory mutation system technique, and the expression of VEGFA, VEGFR1 and VEGFR2 was analyzed using immunohistochemistry in 204 patients with lung adenocarcinoma. Associations between EGFR/KRAS mutational status and VEGFA, VEGFR1, and VEGFR2 expression was analyzed using Pearson chi(2) tests. It was revealed that EGFR 21 exon (P=0.033) and EGFR 20 exon (P=0.002) mutated tumors exhibited a significantly higher level of expression of VEGFA. EGFR 21 exon mutant tumors additionally demonstrated a significantly higher level of co-expression of VEGFA and VEGFR1 (P<0.001). EGFR 19 exon mutation was significantly associated with low levels of VEGFR1 (P=0.008). KRAS mutation was significantly associated with a high level of co-expression of VEGFA, VEGFR1 and VEGFR2 (P=0.035), but no such association with the individual expression of VEGFA, VEGFR1 or VEGFR2 was identified. However, neither KRAS or EGFR mutations exhibited an association with the expression of VEGFR2. The present study may help in the treatment of various patients with KRAS or subtype of EGFR mutation with anti-angiogenesis therapy.