Increased vascular endothelial growth factor expression, CD3-positive cell infiltration, and oxidative stress in premalignant lesions of the cervix.
BACKGROUND
Vascular endothelial growth factor (VEGF) plays an important role in cervical intraepithelial neoplasia (CIN) progression. The occurrence of leukocytes has been documented in CIN; however, their role in VEGF production remains unknown. Oxidative stress has been involved in the progression of malignant neoplasias, but to the authors' knowledge tissue oxidative stress in CIN has not been documented. The objective of the current study was to investigate the expression of VEGF, leukocyte infiltration, leukocyte VEGF expression, and nitrogen/oxygen metabolism in cervical tissues from patients with CIN.


METHODS
Indirect immunofluorescence was used to study the expression of VEGF and leukocyte infiltration in cervical samples from 55 patients with CIN and 7 normal controls. Superoxide anion (O(2) (-)) expression was determined by a cytochemical method, and tissue and serum nitric oxide by the Griess reaction. Human papillomavirus (HPV) DNA and HPV types were identified by the hybrid capture 2 HPV DNA test.


RESULTS
Increased expression of VEGF was observed related to the progression of CIN. A significant increment of CD3 lymphocytes was found in CIN type 3 (CIN 3) and coexpression of CD3/VEGF and monocyte-macrophage/VEGF in CIN 2 and 3. Increased O(2) (-)-positive cells were found in CIN 2 and 3; however, tissue nitrate-nitrite content remained similar to controls. The incidence of HPV infection was 16% in patients with CIN. No significant differences were observed in the values of HPV-positive or HPV-negative patients.


CONCLUSIONS
Different factors leading to cervical neoplasia progression may be involved in the evolution of CIN, and the presence of these factors is most likely not related to the HPV infection status.
Carrero
Yenddy
Y
Regional Laboratory of Virological Reference, Zuila University, Maracaibo, Venezuela.
Callejas
Diana
D
Alaña
Freddy
F
Silva
Chiquinquirá
C
Mindiola
Raimy
R
Mosquera
Jesús
J
D052685:Alphapapillomavirus / Q000235:genetics; D017252:CD3 Complex / Q000378:metabolism*; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating; D018384:Oxidative Stress; D030361:Papillomavirus Infections / Q000150:complications; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D002578:Uterine Cervical Dysplasia / Q000276:immunology* / Q000378:metabolism* / Q000821:virology
D017252:CD3 Complex; D004279:DNA, Viral; D042461:Vascular Endothelial Growth Factor A