Expression of p53, inducible nitric oxide synthase and vascular endothelial growth factor in gastric precancerous and cancerous lesions: correlation with clinical features.
BACKGROUND
The growth and metastasis of tumors depend on the development of an adequate blood supply via angiogenesis. Recent studies indicate that the inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF) and the tumor suppressor p53 are fundamental play-markers of the angiogenic process. Overexpression of iNOS and VEGF has been shown to induce angiogenesis in tumors. P53 suppresses angiogenesis by down-regulating VEGF and iNOS. The correlation of expression of p53, VEGF and iNOS and clinical features in gastric carcinogenesis, however, has not been well characterized.


METHODS
The expression of p53, iNOS and VEGF in gastric precancerous and cancerous lesions and its relation with the clinical features was determined with immunohistochemistry (avidin-biotin-peroxidase complex method) on 55 randomly selected GC patients and 60 symptom-free subjects from the mass survey in the high-incidence area for GC in Henan, northern China.


RESULTS
The positive immunostaining rates for p53, iNOS and VEGF in gastric carcinomas were 51%, 44% and 51%, respectively, and correlated well with TNM stages, but did not show significant difference among the groups with different degrees of gastric wall invasion depth by GC. A positive immunostaining reaction for the iNOS protein was significantly correlated with lymph node metastasis (p = 0.019; Spearman correlation coefficient). P53 protein accumulation was higher in the poorly-differentiated gastric carcinoma than in well-differentiated one. In gastric biopsies, no positive immunostaining was observed for p53, iNOS and VEGF in the histologically normal tissue and chronic superficial gastritis (CSG). However, p53, iNOS and VEGF positive immunostaining was observed in the tissues with different severities of lesions of chronic atrophic gastritis (CAG), intestinal metaplasia (IM) and dysplasia (DYS), and the positive rates increased with the lesion progression from CAG to IM to DYS. A high coincidental positive and negative immunostaining rate for p53, iNOS and VEGF was observed both in biopsy samples with CAG, IM and DYS from the symptom-free subjects and in gastric cancer tissue from the GC patients.


CONCLUSIONS
The present results indicated that p53 protein accumulation and increased expression of iNOS and VEGF might be responsible for gastric carcinogenesis and tumor aggressiveness of gastric cancer.
Feng
Chang Wei
CW
Laboratory for Cancer Research, College of Medicine, Zhengzhou University, Zhengzhou, Henan, China. ldwang@371.net
Wang
Li Dong
LD
Jiao
Lian Hua
LH
Liu
Bin
B
Zheng
Shu
S
Xie
Xin Ji
XJ
D000230:Adenocarcinoma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D002681:China / Q000453:epidemiology; D016228:Endothelial Growth Factors / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005753:Gastric Mucosa / Q000737:chemistry / Q000166:cytology / Q000473:pathology / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism*; D008222:Lymphokines / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000276:immunology / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D011230:Precancerous Conditions / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D013274:Stomach Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D016159:Tumor Suppressor Protein p53 / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II