Upregulation of nuclear factor-κB (NF-κB) 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

M. Branca, C. Giorgi, M. Ciotti, D. Santini, L. Di Bonito, S. Costa, A. Benedetto, D. Bonifacio, P. Di Bonito, P. Paba, L. Accardi, L. Mariani, M. Ruutu, S. Syrjänen, C. Favalli, Kari Syrjänen

Research output: Contribution to journalArticle

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Abstract

Nuclear factor-κB (NF-κB) 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-κB 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-κB, 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-κB expression was associated with CIN3/cancer at OR 3.55 (95% CI, 1.79-7.05), while nuclear NF-κB 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-κB 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-κB is significantly associated with progression to CIN3 and cancer. This is paralleled by only a slight increase in nuclear expression of NF-κB, which could be explained by the mechanisms whereby HR-HPVs escape from the transcriptional control of NF-κB, i.e., E7-mediated impaired nuclear translocation of cytoplasmic NF-κB, and E6-conditioned attenuated NF-κB (p65)-dependent transcriptional activity.

Original languageEnglish
Pages (from-to)555-563
Number of pages9
JournalDiagnostic Cytopathology
Volume34
Issue number8
DOIs
Publication statusPublished - Aug 2006

Fingerprint

Cervical Intraepithelial Neoplasia
Uterine Cervical Neoplasms
Up-Regulation
Squamous Cell Carcinoma
Neoplasms
Polymerase Chain Reaction
Staining and Labeling
Therapeutics
Genes

Keywords

  • Cervical cancer
  • CIN
  • CIN treatment
  • Nf-κB
  • Oncogenic human papillomavirus
  • Persistence
  • Prognosis
  • Virus clearance

ASJC Scopus subject areas

  • Anatomy

Cite this

Upregulation of nuclear factor-κB (NF-κB) 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.; Syrjänen, S.; Favalli, C.; Syrjänen, Kari.

In: Diagnostic Cytopathology, Vol. 34, No. 8, 08.2006, p. 555-563.

Research output: Contribution to journalArticle

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, Syrjänen, S, Favalli, C & Syrjänen, K 2006, 'Upregulation of nuclear factor-κB (NF-κB) 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, vol. 34, no. 8, pp. 555-563. https://doi.org/10.1002/dc.20514
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. ; Syrjänen, S. ; Favalli, C. ; Syrjänen, Kari. / Upregulation of nuclear factor-κB (NF-κB) 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. In: Diagnostic Cytopathology. 2006 ; Vol. 34, No. 8. pp. 555-563.
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AU - Branca, M.

AU - Giorgi, C.

AU - Ciotti, M.

AU - Santini, D.

AU - Di Bonito, L.

AU - Costa, S.

AU - Benedetto, A.

AU - Bonifacio, D.

AU - Di Bonito, P.

AU - Paba, P.

AU - Accardi, L.

AU - Mariani, L.

AU - Ruutu, M.

AU - Syrjänen, S.

AU - Favalli, C.

AU - Syrjänen, Kari

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N2 - Nuclear factor-κB (NF-κB) 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-κB 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-κB, 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-κB expression was associated with CIN3/cancer at OR 3.55 (95% CI, 1.79-7.05), while nuclear NF-κB 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-κB 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-κB is significantly associated with progression to CIN3 and cancer. This is paralleled by only a slight increase in nuclear expression of NF-κB, which could be explained by the mechanisms whereby HR-HPVs escape from the transcriptional control of NF-κB, i.e., E7-mediated impaired nuclear translocation of cytoplasmic NF-κB, and E6-conditioned attenuated NF-κB (p65)-dependent transcriptional activity.

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KW - Oncogenic human papillomavirus

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