The expression of epidermal growth factor receptor, vascular endothelial growth factor, matrix metalloproteinase-2, and cyclooxygenase-2 in relation to human papilloma viral load and persistence of human papillomavirus after conization with negative margins

Authors

  • S.H. SONG,

    1. *Departments of Obstetrics and Gynecology and †Pathology, School of Medicine, Korea University, Seoul, Republic of Korea
    Search for more papers by this author
  • J.K. LEE,

    1. *Departments of Obstetrics and Gynecology and †Pathology, School of Medicine, Korea University, Seoul, Republic of Korea
    Search for more papers by this author
  • J.Y. HUR,

    1. *Departments of Obstetrics and Gynecology and †Pathology, School of Medicine, Korea University, Seoul, Republic of Korea
    Search for more papers by this author
  • I. KIM,

    1. *Departments of Obstetrics and Gynecology and †Pathology, School of Medicine, Korea University, Seoul, Republic of Korea
    Search for more papers by this author
  • H.S. SAW,

    1. *Departments of Obstetrics and Gynecology and †Pathology, School of Medicine, Korea University, Seoul, Republic of Korea
    Search for more papers by this author
  • Y.K. PARK

    Corresponding author
    1. *Departments of Obstetrics and Gynecology and †Pathology, School of Medicine, Korea University, Seoul, Republic of Korea
      Address correspondence and reprint requests to: Yong Kyun Park, MD, PhD, Department of Obstetrics and Gynecology, Korea University School of Medicine, Guro Hospital, Guro-Dong, Guro-Gu, Seoul 152-703, Republic of Korea. Email: ysbmls@yahoo.co.kr
    Search for more papers by this author

  • The authors declare that there are no potential conflicts of interest.

Address correspondence and reprint requests to: Yong Kyun Park, MD, PhD, Department of Obstetrics and Gynecology, Korea University School of Medicine, Guro Hospital, Guro-Dong, Guro-Gu, Seoul 152-703, Republic of Korea. Email: ysbmls@yahoo.co.kr

Abstract

The aim of this study was to investigate the correlations between human papillomavirus (HPV) load and vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), matrix metalloproteinase-2 (MMP-2), and cyclooxygenase-2 (COX-2), and to identify biomarkers that may predict high-risk HPV clearance or persistence after conization with negative margins. The following samples were analyzed: 77 paraffin-embedded specimens from patients with cervical intraepithelial neoplasia (CIN), including 27 CIN 2 conization specimens and 50 CIN 3 conization specimens. Immunohistochemical analysis was performed with antibodies to VEGF, EGFR, MMP-2, and COX-2. Hybrid capture II testing was used to detect HPV DNA. VEGF expression was significantly associated with HPV load (ρ= 0.27186, P= 0.0191), while COX-2 expression was significantly and inversely associated with HPV load (ρ=−0.34309, P= 0.0028). In univariate analysis, HPV load (P= 0.0112) and VEGF expression (P= 0.0274) were significantly associated with high-risk HPV clearance or persistence after conization with negative margins. In multiple regression analysis, high viral load (relative light unit/positive control > 500) and positive VEGF expression were significantly associated with high-risk HPV persistence after conization with negative margins (odds ratio [OR]: 9.915, CI: 1.891–51.994; OR: 6.661, CI: 1.208–36.722, respectively). In conclusion, VEGF expression is related to HPV load, while COX-2 expression is inversely related to HPV load, and immunohistochemical analysis of VEGF expression and HPV viral load are a significant and an independent prognostic indicator of high-risk HPV persistence after conization with negative margins.

Ancillary