Expression of vascular endothelial growth factor in the progression of cervical neoplasia and its relation to angiogenesis and p53 status.
OBJECTIVE
To evaluate vascular endothelial growth factor (VEGF) expression in the successive steps of cervical neoplasia and to determine its correlation with angiogenesis and p53 status.


METHODS
Immunohistochemical staining with a VEGF monoclonal antibody was performed on a total of 161 cervical specimens representing 12 normal epithelium, 33 cervical intraepithelial neoplasia (CIN) 1, 30 CIN 3 and 86 squamous cell carcinomas. Microvessels were immunohistochemically labeled with an antibody to CD34. Computerized image analysis was used to evaluate microvessel density (MVD). p53 Status was determined by immunohistochemistry and direct sequencing of exons 5-8 of the p53 gene.


RESULTS
VEGF expression progressively increased along the continuum from normal epithelium to squamous cell carcinoma (P < .05). MVD increased significantly with cervical neoplasia progression, from normal epithelium, through CIN, to squamous cell carcinoma (P < .001). A strong correlation was observed between VEGF expression and MVD (P < .001). p53 Protein expression was not detected in the normal epithelium or in CIN 1, while 3 (10%) of 30 CIN 3 and 28 (33%) of 86 squamous cell carcinomas were positive for p53. VEGF expression correlated statistically with p53 protein expression (P < .001). In double VEGF- and p53-stained sections, the 2 markers were generally expressed in the same tumor cells. Of the 4 p53 gene mutations, 3 exhibited strong VEGF expression, and 1 exhibited moderate VEGF expression. VEGF expression did not correlate significantly with outcome variables in patients with squamous cell carcinoma.


CONCLUSIONS
Our results suggest that VEGF expression is involved in the promotion of angiogenesis in cervical neoplasia and that p53 is likely to be involved in the regulation of VEGF expression.
Lee
Ji Shin
JS
Department of Pathology, Seonam University College of Medicine, 720 Kwangchi-Dong, Namwon, Chollabuk-Do, 590-711, South Korea.
Kim
Hyung Seok
HS
Park
Jong Tae
JT
Lee
Min Cheol
MC
Park
Chang Soo
CS
D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000378:metabolism* / Q000601:surgery; D005260:Female; D016158:Genes, p53; D006801:Humans; D007044:Hysterectomy; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D009389:Neovascularization, Pathologic; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000601:surgery; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*; D002578:Uterine Cervical Dysplasia / Q000098:blood supply / Q000378:metabolism* / Q000601:surgery
D016159:Tumor Suppressor Protein p53; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A