Aberrant p53 expression correlates with expression of vascular endothelial growth factor mRNA and interleukin-8 mRNA and neoangiogenesis in non-small-cell lung cancer.
OBJECTIVE
To evaluate interactions between expressions of tumor suppressor gene p53 and angiogenic factors vascular endothelial cell growth factor (VEGF) and interleukin-8 (IL-8) and their effect on tumor angiogenesis and patient prognosis in non--small-cell lung cancer (NSCLC).


METHODS
p53, VEGF, IL-8, and the microvessel endothelium were immunostained, and VEGF and IL-8 mRNA expression were quantified using the real-time quantitative reverse-transcription polymerase chain reaction in 65 NSCLC surgical specimens. Aberrant p53 expression was correlated with VEGF and IL-8 mRNA expression, microvessel count (MVC), other clinical-pathologic variables, and patients' survival.


RESULTS
Tumors with high aberrant p53 expression showed significantly higher VEGF and IL-8 mRNA expression and MVC than those with low aberrant p53 expression (P <.001). When tested as a continuous variable, aberrant p53 expression correlated strongly and positively with VEGF and IL-8 mRNA expression and MVC (P <.0001). Tumors with high aberrant p53 expression were associated with mediastinal or distant lymph node metastasis (P =.006). Survival and postoperative relapse time were significantly shorter in patients with high aberrant p53 expression tumors than in those with low aberrant expression tumors (P <.0001). A significant difference in survival was also seen between patients with high and low tumoral VEGF mRNA expression and between those with high and low tumoral IL-8 mRNA expression (P <.0001).


CONCLUSIONS
We report here for the first time that aberrant p53 expression is strongly positively correlated with VEGF mRNA and IL-8 mRNA expression in NSCLC. This result indicates that aberrant p53 expression may play a significant role in regulation of VEGF and IL-8 expression and be involved in controlling angiogenesis and explains the adverse prognosis of cancers with high aberrant p53 expression.
Yuan
Ang
A
Division of Chest Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei.
Yu
Chong-Jen
CJ
Luh
Kwen-Tay
KT
Kuo
Sow-Hsong
SH
Lee
Yung-Chie
YC
Yang
Pan-Chyr
PC
D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology*; D004273:DNA, Neoplasm / Q000235:genetics; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008222:Lymphokines / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D004273:DNA, Neoplasm; D016228:Endothelial Growth Factors; D016209:Interleukin-8; D008222:Lymphokines; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors