Glomeruloid microvascular proliferation is superior to intratumoral microvessel density as a prognostic marker in non-small cell lung cancer.
Glomeruloid microvascular proliferation (GMP) is a focal proliferative budding of endothelial cells (ECs) resembling a renal glomerulus. Whereas some experimental and clinical studies have suggested recently that GMPs indicate an aggressive angiogenic phenotype, the incidence and clinical significance of GMPs remains unclear. Thus, we conducted a retrospective study on GMPs in a total of 236 patients with completely resected pathological (p-) stage I-IIIA NSCLC. ECs were highlighted with immunohistochemical staining using an anti-CD34 antibody, and GMPs were defined as focal glomerulus-like aggregates of closely associated and multilayer CD34-positive ECs. Expression of vascular endothelial growth factor, angiopoietin (Ang)-1, and Ang-2 was also examined immunohistochemically. GMPs were positive in 60 (25.4%) patients, and the incidence was not correlated with age, gender, histological type, or p-stage. The mean intratumoral microvessel densities for GMP-negative tumor and GMP-positive tumor were 178.2 and 184.1, respectively, showing that the incidence of GMPs was not correlated with intratumoral microvessel density (P = 0.676). There was no correlation between vascular endothelial growth factor expression and the incidence of GMPs, but GMPs were more frequently seen in Ang-1-positive tumor than in Ang-1-negative tumor. The 5-year survival rate of GMP-positive patients was 54.2%, which was significantly lower than that of GMP-negative patients (72.3%; P = 0.016). The 5-year survival rate of higher-MVD patients (71.5%) seemed to be lower than that of the lower-MVD patients (63.7%), but the difference did not reach a statistical significance (P = 0.137). A multivariate analysis confirmed that the presence of GMPs was a significant prognostic factor (P = 0.003), whereas MVD was not. In conclusion, GMPs indicate an aggressive angiogenic phenotype associated with a poor prognosis in NSCLC.
Tanaka
Fumihiro
F
Department of Thoracic Surgery, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan. ftanaka@kuhp.kyoto-u.ac.jp
Oyanagi
Hiroki
H
Takenaka
Kazumasa
K
Ishikawa
Shinya
S
Yanagihara
Kazuhiro
K
Miyahara
Ryo
R
Kawano
Yozo
Y
Li
Mio
M
Otake
Yosuke
Y
Wada
Hiromi
H
D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply* / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000473:pathology*; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate