Up-regulation of VEGF, c-fms and COX-2 expression correlates with severity of cervical cancer precursor (CIN) lesions and invasive disease

Luciano S. Hammes, Rajeshwar Rao Tekmal, Paulo Naud, Maria Isabel Edelweiss, Nameer Kirma, Philip T. Valente, Kari J. Syrjänen, João Sabino Cunha-Filho

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


Objectives: To describe the expression of vascular endothelial growth factor (VEGF), proto-oncogene macrophage colony-stimulating factor receptor (c-fms) and cyclooxygenase-2 (COX-2) in cervical carcinogenesis and to analyze the correlation of VEGF with c-fms and COX-2 expression. Methods: In this study, 26 cases of benign cervix, 28 low-grade cervical intraepithelial neoplasia (CIN; CIN 1), 30 high-grade CIN (CIN 2/3) and 28 squamous cervical carcinomas (SCC) were examined by immunohistochemistry (IHC) and analysis was performed separately for epithelium and stroma. Results: Positive epithelial expressions in normal cervix, low-grade CIN, high-grade CIN and SCC were, respectively: VEGF - 11.5%, 39.3%, 53.3% and 75% (P < 0.001); c-fms - 0%, 10.7%, 40% and 67.9% (P < 0.001); COX-2 - 7.7%, 39.3%, 80% and 100% (P < 0.001). Stromal VEGF expression was higher than epithelial expression in all CIN grades and was also associated with the lesion grade, while c-fms and COX-2 stromal expression was weak. VEGF expression was statistically correlated to c-fms and COX-2 expression in high-grade CIN (P = 0.020 and P = 0.027, respectively) and SCC (P = 0.015 and P = 0.005, respectively). Conclusions: On the basis of our findings, these factors may participate in the development and progression of CIN lesions, with possible interaction of c-fms and COX-2 on VEGF expression, and may be potential molecular targets for studies of cervical cancer prevention and treatment.

Original languageEnglish (US)
Pages (from-to)445-451
Number of pages7
JournalGynecologic Oncology
Issue number3
StatePublished - Sep 2008


  • Angiogenesis
  • Cervical cancer
  • Cervical intraepithelial neoplasia
  • Cyclooxygenase-2
  • Macrophage colony-stimulating factor receptor
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology


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