Vascular endothelial growth factor level as a prognostic determinant of small cell lung cancer in Japanese patients.
OBJECTIVE
To clarify the clinical significance of vascular endothelial growth factor (VEGF) in Japanese patients with small cell lung cancer (SCLC).


METHODS
We measured serum VEGF levels using an enzyme-linked immunosorbent assay in 45 patients with SCLC before treatment and in 38 patients with benign pulmonary disease and in 32 healthy subjects (71 non-malignant subjects). VEGF immunostaining was performed in tissue biopsies obtained from 23 SCLC patients during bronchoscopic examination.


RESULTS
Median serum VEGF level was 332 pg/ml in patients with SCLC and 160 pg/ml in non-malignant subjects, respectively. The 95% cut-off level to exclude non-malignant subjects was 500 pg/ml. An elevated VEGF level (>500 pg/ml) was found more frequently in patients with extensive disease of SCLC than in those with the limited disease (p<0.01). A significant positive correlation was found between the serum VEGF level and platelet count in SCLC patients (r=0.389; p=0.0083). Serum VEGF level also correlated with serum lactate dehydrogenase in SCLC patients (r=0.381; p=0.0098). However, it did not correlate with serum neuron-specific enolase and pro-gastrin-releasing peptide level. Patients with the elevated VEGF levels had significantly shorter progression-free time than those with the normal VEGF levels (p<0.05). Patients with the elevated VEGF levels had a significantly shorter overall survival time than those with the normal VEGF levels in univariate survival analysis (p<0.05). Further, the elevated VEGF level remained as a significant determinant of poor survival in multivariate analysis (p<0.01). Serum VEGF level was significantly higher in patients with positive VEGF protein immunoreactivity in tumor tissue in SCLC.


CONCLUSIONS
Elevated serum VEGF levels were associated with poor outcome in SCLC.
Hasegawa
Yukihiro
Y
Second Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki.
Takanashi
Shingo
S
Okudera
Koichi
K
Kumagai
Mika
M
Hayashi
Akihito
A
Morimoto
Takeshi
T
Okumura
Ken
K
D000368:Aged; D018288:Carcinoma, Small Cell / Q000097:blood*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008175:Lung Neoplasms / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010976:Platelet Count; D011379:Prognosis; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
D042461:Vascular Endothelial Growth Factor A; D007770:L-Lactate Dehydrogenase