title: Cell binding isoforms of vascular endothelial growth factor-A (VEGF189) contribute to blood flow-distant metastasis of pulmonary adenocarcinoma.
abstract: Vascular endothelial growth factor A (VEGF-A) has two kinds of isoforms depending on cellular binding domains. VEGF189 is the largest molecule with the strongest cellular binding ability, and is thought to be most potent for vascularization in various cancers. This study aims to clear the clinicopathological characteristics of VEGF189 in the pulmonary adenocarcinoma. We finely and quantitatively examined the expression of VEGF-A isoforms (VEGF121, VEGF165 and VEGF189) by real-time polymerase chain reaction in a total of 100 pulmonary adenocarcinomas resected by surgical operation. The VEGF isoform expression status was analyzed on clinicopathological features including stromal vascularization, vascular involvement, distant metastasis, lymph nodal metastasis, postoperative relapse time and prognosis of long-term observation periods. All the pulmonary adenocarcinomas showed significant expression of VEGF-A. Twenty-two cases with the adenocarcinomas overexpressing VEGF-A significantly showed earlier postoperative relapse and poorer prognosis between 5- to 15-year periods (p = 0.0093 and p = 0.0240, Kaplan Meier, log-rank test). The expression levels of VEGF189 increased in 13% of the pulmonary adenocarcinoma. These 13 cases with increased VEGF189 expression significantly showed higher distant metastases, earlier postoperative relapse, and poorer prognosis (p = 0.0006, Fisher's test; p = 0.0016 and p = 0.0084, Kaplan Meier, log-rank test) than the other 87 cases. The 13 lung cancers with VEGF189 overexpression also showed increased vessel counts, areas (p = 0.0091 and p < 0.0001, Mann-Whitney U test) and enhanced venous involvement (p = 0.0056, Fisher's test). The cellular binding isoform VEGF189 confers pulmonary adenocarcinoma patients with poorer prognosis with distant metastasis via blood flow.
authors.affiliation: Department of Pathology, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa 259-1193, Japan.
authors.forename: Masatake
authors.initials: M
authors.lastname: Nishi
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Abe
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Tomii
authors.forename: Hideo
authors.initials: H
authors.lastname: Tsukamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kijima
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yamazaki
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ohnishi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Iwasaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inoue
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Ueyama
authors.forename: Masato
authors.initials: M
authors.lastname: Nakamura
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000401:mortality / Q000473:pathology* / Q000556:secondary; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D020033:Protein Isoforms; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000235:genetics / Q000502:physiology*
chemical_list: D020033:Protein Isoforms; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A