Vascular endothelial growth factor expression in progression of cervical cancer: correlation with thymidine phosphorylase expression, angiogenesis, tumor cell proliferation, and apoptosis.
BACKGROUND
Vascular endothelial growth factor (VEGF) has been linked not only to angiogenic activity but also to thymidine phosphorylase (TP), rapid tumor growth, and inhibition of apoptotic cell death. Our purpose was to examine how VEGF expression affect these factors in cervical cancer at varying stages of progression.


METHODS
VEGF expression, TP expression, the microvessel count (reflected by factor VIII-related antigen), and proliferating cell nuclear antigen (PCNA) were assessed immunohistochemically in 19 specimens of normal cervical epithelium, 35 of carcinoma in situ (CIS), 34 of microinvasive carcinoma (MIC), and 34 of invasive cervical squamous cell carcinoma (SCC). Apoptosis was evaluated by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method.


RESULTS
VEGF expression progressively increased along a continuum from normal epithelium to invasive SCC (P < 0.0001). VEGF expression significantly correlated with TP expression and PCNA index (P < 0.01 and P < 0.0001, respectively). In analyses within histological stages, VEGF expression significantly correlated with the PCNA index in CIS and MIC (P < 0.01 and P < 0.05, respectively), but not in invasive SCC. The PCNA index for combined analysis of VEGF and TP expression was similar to that for VEGF expression alone. VEGF expression tended to correlate with microvessel count, however, the difference was not significant (P = 0.09). No significant correlation was observed between VEGF expression and the apoptotic index.


CONCLUSIONS
VEGF expression may stimulate tumor cell proliferation in the early stages of cervical cancer, and may be responsible for cervical tumorigenesis.
Fujiwaki
R
R
Department of Obstetrics and Gynecology, Shimane Medical University, Izumo, Japan. fuji39@shimane-med.ac.jp
Hata
K
K
Iida
K
K
Maede
Y
Y
Miyazaki
K
K
D017209:Apoptosis; D002278:Carcinoma in Situ / Q000097:blood / Q000473:pathology* / Q000601:surgery; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000473:pathology* / Q000601:surgery; D002455:Cell Division; D018450:Disease Progression; D016228:Endothelial Growth Factors / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008222:Lymphokines / Q000032:analysis*; D008833:Microcirculation / Q000473:pathology; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D012189:Retrospective Studies; D017154:Stromal Cells / Q000473:pathology; D013939:Thymidine Phosphorylase / Q000032:analysis*; D002583:Uterine Cervical Neoplasms / Q000098:blood supply / Q000473:pathology* / Q000601:surgery; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D018809:Proliferating Cell Nuclear Antigen; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D013939:Thymidine Phosphorylase