Local expression of interferon-alpha and interferon receptors in cervical intraepithelial neoplasia

Cancer Immunol Immunother. 2009 Dec;58(12):2003-10. doi: 10.1007/s00262-009-0707-6. Epub 2009 Apr 18.

Abstract

Purpose: The present study evaluated mRNA expression of interferon-alpha (IFN-alpha), IFN-alpha receptor subunits (IFNAR-1 and IFNAR-2) and an IFN-stimulated gene encoding the enzyme 2',5'-oligoadenylate synthetase (2'5'OAS) in biopsies on patients with varying grades of cervical intraepithelial neoplasia (CIN I, II and III).

Methods: Uterine cervix biopsies were collected from women with CIN I, II and III (n = 28) and controls without CIN lesions or human papilloma virus (HPV) infection (n = 17). The presence of high and low-risk HPV DNA was determined using hybrid capture. The mRNA levels of IFNAR-1, IFNAR-2, IFN-alpha and 2'5'OAS were determined by RT-PCR with specific primers.

Results: The control group exhibited a greater frequency of IFNAR-1 expression (10/17; 58.3%) than the CIN samples (4/28; 14.2%) (P = 0.0018), while, the expression of IFNAR-2 was also greater in the control samples (11/17; 64.7%) than in the patients with lesions (2/28; 7.1%) (P = 0.0018). Importantly, simultaneous expression of both receptors was observed only in the control group (8/17; 47.0%) (P = 0.0001). Among the CIN samples, there was one case of low expression of mRNA of IFNAR-1 and IFNAR-2. IFN-alpha was present in 14.2% (4/28) of the CIN samples but was not expressed in the control group. mRNA 2'5'OAS were expressed in 28.5% (8/28) of the CIN samples and 11.7% (2/17) of the control samples (not statistically significant). Fifty percent (14/28) of the CIN samples were positive for HPV DNA.

Conclusions: Cervical biopsy samples from control women or those without neoplasia or HPV infection displayed higher IFN-alpha receptor expression than those with CIN, while simultaneous expression of both IFN-alpha receptor subunits was found only in the control group. There was no significant difference in mRNA expression of IFN-alpha and 2'5'OAS between the control and CIN groups. Then we concluded that the samples obtained from patients with CIN present low levels of the IFN-alpha receptor mRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2',5'-Oligoadenylate Synthetase / biosynthesis
  • 2',5'-Oligoadenylate Synthetase / genetics
  • Adolescent
  • Case-Control Studies
  • DNA, Viral / analysis
  • Female
  • Humans
  • Interferon-alpha / biosynthesis*
  • Interferon-alpha / genetics
  • Middle Aged
  • Papillomaviridae / genetics
  • Papillomavirus Infections / immunology
  • Papillomavirus Infections / virology
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Receptor, Interferon alpha-beta / biosynthesis*
  • Receptor, Interferon alpha-beta / genetics
  • Signal Transduction
  • Uterine Cervical Dysplasia / enzymology
  • Uterine Cervical Dysplasia / genetics
  • Uterine Cervical Dysplasia / immunology*
  • Uterine Cervical Dysplasia / virology
  • Uterine Cervical Neoplasms / enzymology
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / immunology*
  • Uterine Cervical Neoplasms / virology
  • Young Adult

Substances

  • DNA, Viral
  • IFNAR1 protein, human
  • IFNAR2 protein, human
  • Interferon-alpha
  • RNA, Messenger
  • Receptor, Interferon alpha-beta
  • 2',5'-Oligoadenylate Synthetase