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Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

Nuclear expression of p65 (RelA) in patients receiving post-operative radiotherapy for locally advanced squamous cell carcinoma of the head and neck

Authors: Dirk Rades, Stefan Huttenlocher, Nina D Seibold, Maximilian P Gebhard, Christoph Thorns, Katrin Hasselbacher, Barbara Wollenberg, Steven E Schild

Published in: BMC Cancer | Issue 1/2015

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Abstract

Background

This study investigated the prognostic role of nuclear expression of p65 in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) receiving post-operative radio(chemo)therapy.

Methods

Nuclear p65-expression (H-score ≤50 versus >50) plus twelve characteristics were analyzed in 151 patients for overall survival (OS), metastases-free survival (MFS) and loco-regional control (LRC). Additional characteristics included age, gender, Karnofsky performance score (KPS), pre-radiotherapy hemoglobin levels, tumor site, histological grading, human papilloma virus (HPV)-status, T-classification, N-classification, American Joint Committee on Cancer (AJCC)-stage, extent of resection and concurrent chemotherapy. Univariate analyses were performed with Kaplan-Meier method and log-rank test, multivariate analyses with Cox proportional hazards model.

Results

On univariate analyses, p65-expression had a significant impact on OS (p < 0.001) and LRC (p < 0.001) but not on MFS (p = 0.29). On multivariate analysis, KPS ≥80 (risk ratio [RR] 2.23; p = 0.012), HPV-positivity (RR 5.83; p = 0.020), T1-T2 (RR 1.38; p = 0.048), N0-N2a (RR 2.72; p = 0.005) and complete resection (RR 2.02; p = 0.049) were positively associated with OS; p65-negativity achieved borderline significance (RR 3.02; p = 0.052). Better MFS was associated with KPS ≥80 (RR 2.49; p = 0.015), T1-T2 (RR: 1.74; p = 0.005), N0-N2a (RR: 6.22; p < 0.001) and complete resection (RR 3.43; p = 0.003). Positive associations with LRC were found for p65-negativity (RR 5.06; p = 0.008), T1-T2 (RR: 1.49; p = 0.022), N0-N2a (RR: 2.97; p = 0.004) and favorable tumor site (RR 1.28; p = 0.025).

Conclusions

P65-negativity was significantly associated with improved LRC and achieved borderline significance with respect to improved OS. Thus, p65-expression may be an additional target for novel agents in the treatment of locally advanced SCCHN.
Literature
1.
go back to reference Pignon JP, le Maître A, Maillard E, Bourhis J, MACH-NC Collaborative Group. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol. 2009;92:4–14.CrossRefPubMed Pignon JP, le Maître A, Maillard E, Bourhis J, MACH-NC Collaborative Group. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol. 2009;92:4–14.CrossRefPubMed
2.
go back to reference Blanchard P, Baujat B, Holostenco V, Bourredjem A, Baey C, Bourhis J, et al. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): a comprehensive analysis by tumour site. Radiother Oncol. 2011;100:33–40.CrossRefPubMed Blanchard P, Baujat B, Holostenco V, Bourredjem A, Baey C, Bourhis J, et al. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): a comprehensive analysis by tumour site. Radiother Oncol. 2011;100:33–40.CrossRefPubMed
3.
go back to reference Blanchard P, Bourhis J, Lacas B, Posner MR, Vermorken JB, Hernandez JJ, et al. Taxane-cisplatin-fluorouracil as induction chemotherapy in locally advanced head and neck cancers: an individual patient data meta-analysis of the meta-analysis of chemotherapy in head and neck cancer group. J Clin Oncol. 2013;31:2854–60.CrossRefPubMed Blanchard P, Bourhis J, Lacas B, Posner MR, Vermorken JB, Hernandez JJ, et al. Taxane-cisplatin-fluorouracil as induction chemotherapy in locally advanced head and neck cancers: an individual patient data meta-analysis of the meta-analysis of chemotherapy in head and neck cancer group. J Clin Oncol. 2013;31:2854–60.CrossRefPubMed
4.
go back to reference Dietz A, Rudat V, Conradt C, Weidauer H, Ho A, Moehler T. Prognostic relevance of serum levels of the angiogenic peptide bFGF in advanced carcinoma of the head and neck treated by primary radiochemotherapy. Head Neck. 2000;22:666–73.CrossRefPubMed Dietz A, Rudat V, Conradt C, Weidauer H, Ho A, Moehler T. Prognostic relevance of serum levels of the angiogenic peptide bFGF in advanced carcinoma of the head and neck treated by primary radiochemotherapy. Head Neck. 2000;22:666–73.CrossRefPubMed
5.
go back to reference Rudat V, Stadler P, Becker A, Vanselow B, Dietz A, Wannenmacher M, et al. Predictive value of the tumor oxygenation by means of pO2 histography in patients with advanced head and neck cancer. Strahlenther Onkol. 2001;177:462–8.CrossRefPubMed Rudat V, Stadler P, Becker A, Vanselow B, Dietz A, Wannenmacher M, et al. Predictive value of the tumor oxygenation by means of pO2 histography in patients with advanced head and neck cancer. Strahlenther Onkol. 2001;177:462–8.CrossRefPubMed
6.
go back to reference Seibold ND, Schild SE, Gebhard MP, Noack F, Schröder U, Rades D. Prognosis of patients with locally advanced squamous cell carcinoma of the head and neck. Impact of tumor cell expression of EPO and EPO-R. Strahlenther Onkol. 2013;189:559–65.CrossRefPubMed Seibold ND, Schild SE, Gebhard MP, Noack F, Schröder U, Rades D. Prognosis of patients with locally advanced squamous cell carcinoma of the head and neck. Impact of tumor cell expression of EPO and EPO-R. Strahlenther Onkol. 2013;189:559–65.CrossRefPubMed
7.
go back to reference Rades D, Seibold ND, Hoffmann A, Gebhard MP, Noack F, Thorns C, et al. Impact of the HPV positivity definition on the prognostic value of HPV status in patients with locally advanced squamous cell carcinoma of the head and neck. Strahlenther Onkol. 2013;189:856–60.CrossRefPubMed Rades D, Seibold ND, Hoffmann A, Gebhard MP, Noack F, Thorns C, et al. Impact of the HPV positivity definition on the prognostic value of HPV status in patients with locally advanced squamous cell carcinoma of the head and neck. Strahlenther Onkol. 2013;189:856–60.CrossRefPubMed
8.
go back to reference Balermpas P, Michel Y, Wagenblast J, Seitz O, Sipek F, Rödel F, et al. Nuclear NF-κB expression correlates with outcome among patients with head and neck squamous cell carcinoma treated with primary chemoradiation therapy. Int J Radiat Oncol Biol Phys. 2013;86:785–90.CrossRefPubMed Balermpas P, Michel Y, Wagenblast J, Seitz O, Sipek F, Rödel F, et al. Nuclear NF-κB expression correlates with outcome among patients with head and neck squamous cell carcinoma treated with primary chemoradiation therapy. Int J Radiat Oncol Biol Phys. 2013;86:785–90.CrossRefPubMed
9.
go back to reference Nakayama H, Ikebe T, Beppu M, Shirasuna K. High expression levels of nuclear factor kappaB, IkappaB kinase alpha and Akt kinase in squamous cell carcinoma of the oral cavity. Cancer. 2001;92:3037–44.CrossRefPubMed Nakayama H, Ikebe T, Beppu M, Shirasuna K. High expression levels of nuclear factor kappaB, IkappaB kinase alpha and Akt kinase in squamous cell carcinoma of the oral cavity. Cancer. 2001;92:3037–44.CrossRefPubMed
10.
go back to reference McCarty Jr KS, Miller LS, Cox EB, Konrath J, McCarty Sr KS. Estrogen receptor analyses. Correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies. Arch Pathol Lab Med. 1985;109:716–21.PubMed McCarty Jr KS, Miller LS, Cox EB, Konrath J, McCarty Sr KS. Estrogen receptor analyses. Correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies. Arch Pathol Lab Med. 1985;109:716–21.PubMed
11.
go back to reference Wentzensen N, Knebel-Doeberitz M. Viral cancerogenesis of head and neck tumors. Pathologe. 2004;25:21–30.CrossRefPubMed Wentzensen N, Knebel-Doeberitz M. Viral cancerogenesis of head and neck tumors. Pathologe. 2004;25:21–30.CrossRefPubMed
12.
go back to reference Petersen I, Schewe C, Schlüns K, Dietel M, Speich N, Schmitt C, et al. Inter-laboratory validation of PCR-based HPV detection in pathology specimens. Virchows Arch. 2007;451:701–16.CrossRefPubMed Petersen I, Schewe C, Schlüns K, Dietel M, Speich N, Schmitt C, et al. Inter-laboratory validation of PCR-based HPV detection in pathology specimens. Virchows Arch. 2007;451:701–16.CrossRefPubMed
13.
go back to reference Dorsey K, Agulnik M. Promising new molecular targeted therapies in head and neck cancer. Drugs. 2013;74:315–25.CrossRef Dorsey K, Agulnik M. Promising new molecular targeted therapies in head and neck cancer. Drugs. 2013;74:315–25.CrossRef
14.
go back to reference Simone 2nd CB, Ly D, Dan TD, Ondos J, Ning H, Belard A, et al. Comparison of intensity-modulated radiotherapy, adaptive radiotherapy, proton radiotherapy, and adaptive proton radiotherapy for treatment of locally advanced head and neck cancer. Radiother Oncol. 2011;101:376–82.CrossRefPubMedPubMedCentral Simone 2nd CB, Ly D, Dan TD, Ondos J, Ning H, Belard A, et al. Comparison of intensity-modulated radiotherapy, adaptive radiotherapy, proton radiotherapy, and adaptive proton radiotherapy for treatment of locally advanced head and neck cancer. Radiother Oncol. 2011;101:376–82.CrossRefPubMedPubMedCentral
15.
go back to reference Yang H, Diao LQ, Shi M, Ma R, Wang JH, Li JP, et al. Efficacy of intensity-modulated radiotherapy combined with chemotherapy or surgery in locally advanced squamous cell carcinoma of the head-and-neck. Biologics. 2013;7:223–9.PubMedPubMedCentral Yang H, Diao LQ, Shi M, Ma R, Wang JH, Li JP, et al. Efficacy of intensity-modulated radiotherapy combined with chemotherapy or surgery in locally advanced squamous cell carcinoma of the head-and-neck. Biologics. 2013;7:223–9.PubMedPubMedCentral
16.
go back to reference Jensen AD, Krauss J, Weichert W, Bergmann ZP, Freier K, Debus J, et al. Disease control and functional outcome in three modern combined organ preserving regimens for locally advanced squamous cell carcinoma of the head and neck (SCCHN). Radiat Oncol. 2011;6:122.CrossRefPubMedPubMedCentral Jensen AD, Krauss J, Weichert W, Bergmann ZP, Freier K, Debus J, et al. Disease control and functional outcome in three modern combined organ preserving regimens for locally advanced squamous cell carcinoma of the head and neck (SCCHN). Radiat Oncol. 2011;6:122.CrossRefPubMedPubMedCentral
17.
go back to reference Yoshida K, Sasaki R, Nishimura H, Okamoto Y, Suzuki Y, Kawabe T, et al. Nuclear factor-kappaB expression as a novel marker of radioresistance in early-stage laryngeal cancer. Head Neck. 2010;32:646–55.PubMed Yoshida K, Sasaki R, Nishimura H, Okamoto Y, Suzuki Y, Kawabe T, et al. Nuclear factor-kappaB expression as a novel marker of radioresistance in early-stage laryngeal cancer. Head Neck. 2010;32:646–55.PubMed
18.
go back to reference Quintana A, Avilés FX, Terra X, Alcolea S, Camacho M, Quer M, et al. Overexpression of the nuclear factor-kappa B (p65) in association with local failure in patients with head and neck carcinoma undergong radiotherapy or chemoradiotherapy. Head Neck. 2013;35:370–5.CrossRefPubMed Quintana A, Avilés FX, Terra X, Alcolea S, Camacho M, Quer M, et al. Overexpression of the nuclear factor-kappa B (p65) in association with local failure in patients with head and neck carcinoma undergong radiotherapy or chemoradiotherapy. Head Neck. 2013;35:370–5.CrossRefPubMed
19.
go back to reference Cerezo L, Millan I, Torre A, Aragon G, Otero J. Prognostic factors for survival and tumor control in cervical lymph node metastases from head and neck cancer. A multivariate study of 492 cases. Cancer. 1992;69:1224–34.CrossRefPubMed Cerezo L, Millan I, Torre A, Aragon G, Otero J. Prognostic factors for survival and tumor control in cervical lymph node metastases from head and neck cancer. A multivariate study of 492 cases. Cancer. 1992;69:1224–34.CrossRefPubMed
20.
go back to reference Rades D, Stoehr M, Kazic N, Hakim SG, Walz J, Schild SE, et al. Locally advanced stage IV squamous cell carcinoma of the head and neck: impact of pre-radiotherapy hemoglobin level and interruptions during radiotherapy. Int J Radiat Oncol Biol Phys. 2008;70:1108–14.CrossRefPubMed Rades D, Stoehr M, Kazic N, Hakim SG, Walz J, Schild SE, et al. Locally advanced stage IV squamous cell carcinoma of the head and neck: impact of pre-radiotherapy hemoglobin level and interruptions during radiotherapy. Int J Radiat Oncol Biol Phys. 2008;70:1108–14.CrossRefPubMed
21.
go back to reference Jeremic B, Milicic B. Pretreatment prognostic factors of local recurrence-free survival in locally advanced squamous cell carcinoma of the head and neck treated with radiation therapy with or without concurrent chemotherapy. Am J Clin Oncol. 2008;31:213–8.CrossRefPubMed Jeremic B, Milicic B. Pretreatment prognostic factors of local recurrence-free survival in locally advanced squamous cell carcinoma of the head and neck treated with radiation therapy with or without concurrent chemotherapy. Am J Clin Oncol. 2008;31:213–8.CrossRefPubMed
22.
go back to reference Jeremic B, Milicic B. Pretreatment prognostic factors of survival in patients with locally advanced nonmetastatic squamous cell carcinoma of the head and neck treated with radiation therapy with or without concurrent chemotherapy. Am J Clin Oncol. 2009;32:163–8.CrossRefPubMed Jeremic B, Milicic B. Pretreatment prognostic factors of survival in patients with locally advanced nonmetastatic squamous cell carcinoma of the head and neck treated with radiation therapy with or without concurrent chemotherapy. Am J Clin Oncol. 2009;32:163–8.CrossRefPubMed
23.
go back to reference Rudat V, Wannenmacher M. Role of multimodal treatment in oropharynx, larynx, and hypopharynx cancer. Semin Surg Oncol. 2001;20:66–74.CrossRefPubMed Rudat V, Wannenmacher M. Role of multimodal treatment in oropharynx, larynx, and hypopharynx cancer. Semin Surg Oncol. 2001;20:66–74.CrossRefPubMed
Metadata
Title
Nuclear expression of p65 (RelA) in patients receiving post-operative radiotherapy for locally advanced squamous cell carcinoma of the head and neck
Authors
Dirk Rades
Stefan Huttenlocher
Nina D Seibold
Maximilian P Gebhard
Christoph Thorns
Katrin Hasselbacher
Barbara Wollenberg
Steven E Schild
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1107-2

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