Local expression of interferon-alpha and interferon receptors in cervical intraepithelial neoplasia.
OBJECTIVE
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.
Tirone
Nelson R
NR
Research Institute of Oncology (IPON), Federal University of Triângulo Mineiro (UFTM), Minas Gerais, Brazil.
Peghini
Bethanea C
BC
Barcelos
Ana Cristina M
AC
Murta
Eddie F C
EF
Michelin
Marcia A
MA
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis / Q000235:genetics; D000293:Adolescent; D016022:Case-Control Studies; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000276:immunology / Q000821:virology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D053633:Receptor, Interferon alpha-beta / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D002583:Uterine Cervical Neoplasms / Q000201:enzymology / Q000235:genetics / Q000276:immunology* / Q000821:virology; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000201:enzymology / Q000235:genetics / Q000276:immunology* / Q000821:virology
D004279:DNA, Viral; C507964:IFNAR1 protein, human; C508033:IFNAR2 protein, human; D016898:Interferon-alpha; D012333:RNA, Messenger; D053633:Receptor, Interferon alpha-beta; D015088:2',5'-Oligoadenylate Synthetase