Angiogenesis, cell proliferation and apoptosis in progression of cervical neoplasia.
OBJECTIVE
To investigate changes in angiogenesis, cell proliferation and apoptosis in the successive steps of cervical neoplasia and to analyze their interrelationship.


METHODS
A total of 182 cervical specimens, representing 12 normal epithelium, 33 cervical intraepithelial neoplasia (CIN) 1, 21 CIN 2, 30 CIN 3 and 86 squamous cell carcinomas, were evaluated. The microvessels were immunohistochemically labeled with CD34 antibodies. Computerized image analysis was used to evaluate microvessel density (MVD). The apoptotic cells were visualized by a terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling technique and proliferative cells by staining with Ki-67 antibodies.


RESULTS
One-way analysis of variance showed that the MVD, Ki-67 labeling index and apoptotic index increased significantly with the progression of cervical neoplasia from normal epithelium, through CIN, to carcinoma (P <.001 for each index). All the indices, determined in all 182 cervical tissues, were significantly and positively associated with each other (P < .001 in all cases), with correlation coefficients ranging from .649 to .819. MVD in patients with recurrence or death was significantly higher than in disease-free patients (P < .05).


CONCLUSIONS
The results suggest that tumor progression in the cervical epithelium is accompanied by angiogenesis and an increase in both cell proliferation and apoptosis. Angiogenesis may be a prognostic indicator in patients with squamous cell carcinoma of the cervix.
Lee
Ji Shin
JS
Department of Pathology, Seonam University College of Medicine, Namwon, Korea.
Kim
Hyung Seok
HS
Jung
Jong Jae
JJ
Lee
Min Cheol
MC
Park
Chang Soo
CS
D018952:Antigens, CD34 / Q000032:analysis; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000737:chemistry / Q000556:secondary*; D002455:Cell Division; D002584:Cervix Uteri / Q000033:anatomy & histology / Q000098:blood supply / Q000473:pathology; D004847:Epithelial Cells / Q000166:cytology / Q000473:pathology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000032:analysis; D008833:Microcirculation / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000473:pathology*; D011379:Prognosis; D002583:Uterine Cervical Neoplasms / Q000098:blood supply / Q000737:chemistry / Q000473:pathology*; D002578:Uterine Cervical Dysplasia / Q000098:blood supply / Q000737:chemistry / Q000473:pathology*
D018952:Antigens, CD34; D019394:Ki-67 Antigen