Increased vascular endothelial growth factor expression, CD3‐positive cell infiltration, and oxidative stress in premalignant lesions of the cervix

• Published in: Cancer Vol. 115; no. 16; pp. 3680 - 3688
• Main Authors: Carrero, Yenddy, Callejas, Diana, Alaña, Freddy, Silva, Chiquinquirá, Mindiola, Raimy, Mosquera, Jesús
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.08.2009; Wiley-Blackwell
• Subjects: Alphapapillomavirus - genetics; Biological and medical sciences; CD3 Complex - metabolism; Cervical Intraepithelial Neoplasia - immunology; Cervical Intraepithelial Neoplasia - metabolism; Cervical Intraepithelial Neoplasia - virology; DNA, Viral - analysis; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; Humans; intraepithelial cervical neoplasia; lymphocytes; Lymphocytes, Tumor-Infiltrating; Medical sciences; Oxidative Stress; Papillomavirus Infections - complications; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Tumors; vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; Oxidative stress; Premalignant lesion; lymphocytes; intraepithelial cervical neoplasia; Female genital diseases; Cancerology; Vascular endothelium growth factor; Cervical dysplasia; Cervical intraepithelial neoplasia; vascular endothelial growth factor; Infiltration; Lymphocyte; Uterine cervix diseases
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.24411

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 (O2−) 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 O2−‐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. Cancer 2009. © 2009 American Cancer Society. This study demonstrated increased expression of vascular endothelial growth factor, CD3 lymphocytes, and oxidative stress in tissues from patients with cervical intraepithelial neoplasia.