Upregulation of nuclear factor-B (NF-B) is related to the grade of cervical intraepithelial neoplasia, but is not an independent predictor of high-risk human papillomavirus or disease outcome in cervical cancer

Branca, M., Giorgi, C., Ciotti, M., Santini, D., Di Bonito, L., Costa, S., Benedetto, A., Bonifacio, D., Di Bonito, P., Paba, P., Accardi, L., Mariani, L., Ruutu, M., Syrjanen, S., Favalli, C., Syrjanen, K. and on behalf of the HPV-Pathogen ISS Study Group (2006) Upregulation of nuclear factor-B (NF-B) is related to the grade of cervical intraepithelial neoplasia, but is not an independent predictor of high-risk human papillomavirus or disease outcome in cervical cancer. Diagnostic Cytopathology, 34 8: 555-563. doi:10.1002/dc.20514


Author Branca, M.
Giorgi, C.
Ciotti, M.
Santini, D.
Di Bonito, L.
Costa, S.
Benedetto, A.
Bonifacio, D.
Di Bonito, P.
Paba, P.
Accardi, L.
Mariani, L.
Ruutu, M.
Syrjanen, S.
Favalli, C.
Syrjanen, K.
on behalf of the HPV-Pathogen ISS Study Group
Title Upregulation of nuclear factor-B (NF-B) is related to the grade of cervical intraepithelial neoplasia, but is not an independent predictor of high-risk human papillomavirus or disease outcome in cervical cancer
Journal name Diagnostic Cytopathology   Check publisher's open access policy
ISSN 8755-1039
1097-0339
Publication date 2006-01-01
Sub-type Article (original research)
DOI 10.1002/dc.20514
Volume 34
Issue 8
Start page 555
End page 563
Total pages 9
Place of publication New York
Publisher Wiley
Language eng
Subject 111203 Cancer Genetics
Abstract Nuclear factor-B (NF-B) has a pivotal function in controlling a wide variety of gene functions, and has shown to be constitutively activated in many human cancers. The molecular links of NF-B to oncogenic human papillomavirus (HPV) in cervical intraepithelial neoplasia (CIN) lesions and its prognostic value in cervical cancer (CC) are incompletely understood. As part of our HPV-PathogenISS study, a series of 150 squamous-cell carcinomas (SCCs) and 152 CIN lesions were examined using immunohistochemical staining for NF-B, and tested for HPV using PCR with three primer sets (MY09/11, GP5+/GP6+, and SPF). Follow-up data were available from all SCC patients, and 67 CIN lesions had been monitored with serial PCR for HPV clearance/persistence after cone treatment. Cytoplasmic NF-B expression was associated with CIN3/cancer at OR 3.55 (95% CI, 1.79-7.05), while nuclear NF-B expression had an OR of 21.90 (95% CI, 2.96-161.74) (P = 0.0001). Strong nuclear expression was a rare event (8.8%) also in CC, but it was related to high-risk human papillomavirus (HR-HPV) detection, with OR 2.15 (95% CI, 1.08-4.30) (P = 0.022). This association was confounded, however, by the histological grade (Mantel-Haenszel common OR = 1.46; 95% CI, 0.70-3.03) (P = 0.308). Cytoplasmic or nuclear NF-B expression did not predict clearance/persistence of HR-HPV after treatment of CIN, and neither one proved to be a prognostic predictor in CC. Overexpression of cytoplasmic NF-B is significantly associated with progression to CIN3 and cancer. This is paralleled by only a slight increase in nuclear expression of NF-B, which could be explained by the mechanisms whereby HR-HPVs escape from the transcriptional control of NF-B, i.e., E7-mediated impaired nuclear translocation of cytoplasmic NF-B, and E6-conditioned attenuated NF-B (p65)-dependent transcriptional activity. Diagn. Cytopathol. 2006;34:555-563. © 2006 Wiley-Liss, Inc.
Keyword NF-B
oncogenic human papillomavirus
CIN
cervical cancer
prognosis
virus clearance
persistence
CIN treatment
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
UQ Diamantina Institute Publications
 
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