Prognostic impact of survivin, cyclin D1, integrin beta1, and VEGF in patients with small adenocarcinoma of stage I lung cancer.
The purpose of this study was to investigate the impact of survivin, cyclin D1, integrin beta1, and vascular endothelial growth factor (VEGF) in tumor on survival of patients with small adenocarcinoma of the lung. Seventy-two patients with pathologic stage I resected tumors <2 cm in diameter were entered into the study. Each patient underwent curative surgical resection for lung cancer between July 1992 and November 1999. The resected tumors were subjected to immunostaining for each gene. Thirty-five, 26, 6, and 16 patients had tumors with >10% survivin-, >20% cyclin D1-, >10% integrin beta1-, and >10% VEGF-positive cells, respectively. When the survival of 72 patients was compared according to each gene expression, the overall survival of patients with positive expression of survivin, cyclin D1, and integrin [beta]1 was significantly worse than that of individuals whose tumors had negative expression of each gene. By multivariate analysis controlling for each gene expression, no gene expression was an independent marker of poor prognosis, however, the overall survival of the complex gene expression (2 or more gene-positive) group (n = 35) was significantly worse than that of 0 or 1 gene-positive group (n = 37; log-rank test, P = 0.0011; Wilcoxon test, P = 0.0011). When the association between survival and pathologic factors, including lymphatic invasion, venous invasion, type of bronchioalveolar carcinoma, and complex gene positive expression was analyzed, only complex gene-positive expression was found to be a significant independent factor (hazard ratio = 0.085, P = 0.0299). It can be concluded that multiple increased expression of oncogene is a poor prognostic factor in patients with small adenocarcinoma of the lung.
Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Japan. foshita@kcch.jp
Fumihiro
F
Oshita
Hiroyuki
H
Ito
Mizuki
M
Ikehara
Naoki
N
Ohgane
Nobuyuki
N
Hamanaka
Haruhiko
H
Nakayama
Haruhiro
H
Saito
Kouzo
K
Yamada
Kazumasa
K
Noda
Aki
A
Mitsuda
Yoichi
Y
Kameda
D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins; D011379:Prognosis; D016019:Survival Analysis; D000077022:Survivin; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
C107489:BIRC5 protein, human; D015415:Biomarkers; D051034:Inhibitor of Apoptosis Proteins; D019012:Integrin beta1; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D042461:Vascular Endothelial Growth Factor A; D019938:Cyclin D1