Hostname: page-component-5db58dd55d-jnbmb Total loading time: 0 Render date: 2026-05-25T10:41:34.420Z Has data issue: false hasContentIssue false
  • English
  • Français

Use of multiple biological markers in radiotherapy-treated head and neck cancer

Published online by Cambridge University Press:  14 April 2010

P Silva ,
N J Slevin ,
P Sloan ,
H Valentine ,
D Ryder ,
P Price ,
C M L West  and
J J Homer
P Silva
Affiliation:
School of Cancer & Enabling Sciences, The University of Manchester, Manchester, UK Department of Surgery, Christie Hospital NHS Trust, Manchester, UK Department of Otolaryngology-Head and Neck Surgery, Manchester, UK
N J Slevin
Affiliation:
Department of Clinical Oncology, Christie Hospital NHS Trust, Manchester, UK
P Sloan
Affiliation:
Department of Pathology, Manchester, UK
H Valentine
Affiliation:
School of Cancer & Enabling Sciences, The University of Manchester, Manchester, UK
D Ryder
Affiliation:
Department of Medical Statistics, Christie Hospital NHS Trust, Manchester, UK
P Price
Affiliation:
School of Cancer & Enabling Sciences, The University of Manchester, Manchester, UK
C M L West*
Affiliation:
School of Cancer & Enabling Sciences, The University of Manchester, Manchester, UK
J J Homer
Affiliation:
School of Cancer & Enabling Sciences, The University of Manchester, Manchester, UK Department of Surgery, Christie Hospital NHS Trust, Manchester, UK Department of Otolaryngology-Head and Neck Surgery, Manchester, UK
*
Address for correspondence: Prof Catharine West, Translational Radiobiology Group, School of Cancer and Enabling Sciences, The University of Manchester, Christie Hospital, Manchester M20 4BX, UK. Fax: +44 161 446 8111 E-mail: catharine.west@manchester.ac.uk
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective:

Management of patients with head and neck squamous cell carcinoma is often based on clinical parameters, with little appreciation of the underlying tumour biology. Single biological marker studies fail to acknowledge the complexity of these tumours. Our aim was to define a profile of biological markers associated with outcome.

Design:

This retrospective study involved consecutive patients with oropharyngeal squamous cell carcinoma treated with primary radiotherapy between 1996 and 2001. Pre-treatment biopsies were used to study the immunohistochemical expression of nine biological markers. Markers were chosen to reflect biologically relevant pathways.

Results:

Following analysis of nine markers, a profile of two markers was derived (carbonic anhydrase 9 and major vault protein), the co-expression of which conferred a significantly poor probability of locoregional control. The prognostic effect of these biomarkers in combination was greater than their effect individually.

Conclusion:

Biomarker profiles can be established which highlight large differences in locoregional control. Identifying tumours that express both carbonic anhydrase 9 and major vault protein may facilitate patient selection for more aggressive treatment.

Keywords

Head and Neck NeoplasmsTumour MarkersSquamous Carcinoma

Information

Type
Main Articles
Information
The Journal of Laryngology & Otology , Volume 124 , Issue 6 , June 2010 , pp. 650 - 658
Copyright
Copyright © JLO (1984) Limited 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

Footnotes

Presented at the 7th International Conference on Head and Neck Cancer, 22 July 2008, San Francisco, California, USA.

References

1 Ferlay, J, Bray, F, Pisani, P, Parkin, DM. GLOBOCAN 2002: Cancer Incidence, Mortality and Prevalence Worldwide, vol 5. Lyon: IARC Press, 2004Google Scholar
2 Bernier, J, Bentzen, SM. Altered fractionation and combined radio-chemotherapy approaches: pioneering new opportunities in head and neck oncology. Eur J Cancer 2003;39:560–71CrossRefGoogle ScholarPubMed
3 Lefebvre, JL, Chevalier, D, Luboinski, B, Kirkpatrick, A, Collette, L, Sahmoud, T. Larynx preservation in pyriform sinus surgery: preliminary results of a European Organisation for Research and Treatment of Cancer phase II trial. EORTC Head And Neck Cancer Coop Group. J Natl Cancer Inst 1996;88:890–9CrossRefGoogle Scholar
4 Pignon, JP, Bourhis, J, Domenge, C, Designe, L. Chemotherapy added to locoregional treatment head and neck squamous for cell carcinoma: three meta-analyses of updated individual data. Lancet 2000;355:949–55CrossRefGoogle ScholarPubMed
5 Clark, JR, de Almeida, J, Gilbert, R, Irish, J, Nelligan, P, Gullane, PJ. Primary and salvage (hypo)pharyngectomy: analysis and outcome. Head Neck 2006;28:671–7CrossRefGoogle ScholarPubMed
6 Buffa, FM, Bentzen, SM, Daley, FM, Dische, S, Saunders, MI, Richman, PI, Wilson, GD. Molecular marker profiles predict locoregional control of head and neck squamous cell carcinoma in a randomised trial of continuous hyperfractionated acclerated radiotherapy. Clin Cancer Res 2004;10:3745–54CrossRefGoogle Scholar
7 Eriksen, JG, Buffa, FM, Alsner, J, Steiniche, T, Bentzen, SM, Overgaard, J. Molecular profiles as predictive markers for the effect of overall treatment time of radiotherapy in supraglottic larynx squamous cell carcinomas. Radiother Oncol 2004;72:275–82CrossRefGoogle ScholarPubMed
8 Sly, WS, Hu, PY. Human carbonic anhydrases and carbonic anhydrase deficiencies. Annu Rev Biochem 1995;64:375–401CrossRefGoogle ScholarPubMed
9 Hammerman, PS, Fox, CJ. Beginnings of a signal induction pathway for bioenergetic control of cell survival. Trends Biochem Sci 2004;29:586–92CrossRefGoogle Scholar
10 Fowler, JF. How worthwhile are short schedules in radiotherapy? A series of exploratory calculations. Radiat Oncol 1990;18:165–81CrossRefGoogle ScholarPubMed
11 Grandis, J, Tweardy, D. Elevating levels of TGF-alpha and EGFR are early markers of carcinogenesis in head and neck cancer. Cancer Res 1993;53:3579–84Google ScholarPubMed
12 Shin, DM, Ro, JY, Hong, WK, Hittelman, WN. Dysregulation of EGFR expression in premalignant lesions during head and neck tumourigenesis. Cancer Res 1994;54:3153–9Google Scholar
13 Christensen, ME. The EGF receptor system in head and neck carcinomas and normal tissue. Immunohistochemical and quantitative studies. Dan Med Bull 1998;45:121–34Google ScholarPubMed
14 Panigrahi, AR, Pinder, SE, Chan, SY, Paish, EC, Robertson, JF, Ellis, IO. The role of PTEN and its signalling pathways, including AKT, in breast cancer; an assessment of relationships with other prognostic factors and with outcome. J Pathol 2004;204:93–100CrossRefGoogle ScholarPubMed
15 Kickhoefer, VA, Siva, AC, Kedersha, NL, Inman, EM, Ruland, C, Streuli, M. The 193-kD vault protein, VPARP, is a novel poly(ADP-ribose) polymerase. J Cell Biol 1999;146:917–28CrossRefGoogle ScholarPubMed
16 Schroeijers, AB, Scheffer, GL, Flens, MJ, Meijer, GA, Izquierdo, MA, van der Valk, P et al. Immunohistochemical detection of the human major vault protein LRP with two monoclonal antibodies in formalin-fixed, paraffin-embedded tissues. Am J Pathol 1998;152:373–80Google ScholarPubMed
17 Wilson, GD, Saunders, MI, Dische, S, Richman, PI, Daley, FM, Bentzen, SM. bcl-2 expression in head and neck cancer; an enigmatic prognostic marker. Int J Radiat Oncol Biol Phys 2001;49:435–41CrossRefGoogle ScholarPubMed
18 Sozzi, G, Pastorino, U, Moiraghi, L, Tagliabue, E, Pezzella, F, Ghirelli, C et al. Loss of FHIT function in lung cancer and preinvasive bronchial lesions. Cancer Res 1998;58:5032–7Google ScholarPubMed
19 Withers, HR, Peters, LJ, Taylor, JM, Owen, JB, Morrison, WH, Schultheiss, TE et al. Local control of carcinoma of the tonsil by radiation therapy: an analysis of patterns of fractionation in nine institutions. Int J Radiat Biol 1995;33:549–62CrossRefGoogle ScholarPubMed
20 Gowda, RV, Henk, JM, Mais, KL, Sykes, AJ, Swindell, R, Slevin, NJ. Three weeks radiotherapy for T1 glottic cancer: the Christie and Royal Marsden experience. Radiother Oncol 2003;68:105–11CrossRefGoogle Scholar
21 Turner, SL, Slevin, NJ, Gupta, NK, Swindell, R. Radical external beam radiotherapy for 333 squamous carcinomas of the oral cavity – evaluation of late morbidity and a watch policy for the clinically negative neck. Radiother Oncol 1996;41:21–9Google Scholar
22 Collette, D. Modelling Survival Data in Medical Research, 2nd edn. London: Chapman & Hall, 2004Google Scholar
23 Koukourakis, MI, Giatromanolaki, A, Sivridis, E, Simopoulos, K, Pastorek, J, Wykoff, CC et al. Hypoxia regulated carbonic anhydrase-9 relates to poor vascularisation and resistance of squamous cell head and neck cancer to chemoradiotherapy. Clin Cancer Res 2001;7:3399–403Google ScholarPubMed
24 Koukourakis, MI, Bentzen, SM, Giatromanolaki, A, Wilson, GD, Daley, FM, Saunders, MI et al. Endogenous markers of two separate hypoxia response pathways (hypoxia inducible factor 2 alpha and carbonic anhydrase 9) are associated with radiotherapy failure in head and neck cancer patients recruited into the CHART randomised trial. J Clin Oncol 2006;24:727–35CrossRefGoogle Scholar
25 Beasley, NJ, Wykoff, CC, Watson, PH, Leek, R, Turley, H, Gatter, K et al. Carbonic anhydrase IX, an endogenous hypoxia marker, expression in head and neck squamous cell carcinoma and its relationship to hypoxia, necrosis and microvessel density. Cancer Res 2001;61:5262–7Google ScholarPubMed
26 Kaanders, JH, Wijffels, KI, Marres, HA, Ljungkvist, AS, Pop, LA, van den Hoogen, FJ et al. Pimonidazole binding and tumour vascularity predict for treatment outcome in head and neck cancer. Cancer Res 2002;62:7066–74Google ScholarPubMed
27 Hui, EP, Chan, AT, Pezzella, F, Turley, H, To, KF, Poon, TC et al. Coexpression of hypoxia inducible factors 1 alpha and 2 alpha, carbonic anhydrase IX and vascular endothelial growth factor in nasopharyngeal carcinoma and relationship to survival. Clin Cancer Res 2002;8:2595–604Google Scholar
28 Hoogsteen, IJ, Marres, HA, Wijffels, KI, Rijken, PF, Peters, JP, van den Hoogen, FJ et al. Colocalisation of carbonic anhydrase 9 expression and cell proliferation in head and neck squamous cell carcinoma. Clin Cancer Res 2005;11:97–106CrossRefGoogle Scholar
29 De Schutter, H, Landuyt, W, Verbeken, E, Goethals, L, Hermans, R, Nuyts, S. The prognostic value of the hypoxia markers CA9 and GLUT1 and the cytokines VEGF and IL6 in head and neck squamous cell carcinoma treated by radiotherapy +/- chemotherapy. BMC Cancer 2005;5:42CrossRefGoogle ScholarPubMed
30 Jonathan, RA, Wijffels, KI, Peeters, W, de Wilde, PC, Marres, HA, Merkx, MA et al. The prognostic value of endogenous hypoxia related markers for head and neck squamous cell carcinomas treated with ARCON. Radiother Oncol 2006;79:288–97CrossRefGoogle ScholarPubMed
31 Bache, M, Reddemann, R, Said, HM, Holzhausen, HJ, Taubert, H, Becker, A et al. Immunohistochemical detection of osteopontin in advanced head and neck cancer: prognostic role and correlation with oxygen electrode measurements, hypoxia inducible factor-1-alpha related markers and hemoglobin levels. Int J Radiat Oncol Biol Phys 2006;66:1481–7CrossRefGoogle ScholarPubMed
32 Loncaster, JA, Harris, AL, Davidson, SE, Logue, JP, Hunter, RD, Wycoff, CC et al. Carbonic anhydrase (CA IX) expression, a potential new intrinsic marker of hypoxia: correlations with tumor oxygen measurements and prognosis in locally advanced carcinoma of the cervix. Cancer Res 2001;61:6394–9Google ScholarPubMed
33 Aebersold, DM, Burri, P, Beer, KT, Laissue, J, Djonov, V, Greiner, RH et al. Expression of hypoxia-inducible factor-1alpha: a novel predictive and prognostic parameter in the radiotherapy of oropharyngeal cancer. Cancer Res 2001;61:2911–16Google ScholarPubMed
34 Koukourakis, MI, Giatromanolaki, A, Liberis, V, Sivridis, E. Hypoxia inducible factor 1 alpha and 2 alpha expression is independent of anemia in patients with stage I endometrial cancer. Anticancer Res 2002;22:4137–40Google ScholarPubMed
35 Silva, P, West, CML, Slevin, N, Valentine, H, Ryder, WD, Hampson, L et al. Tumor expression of major vault protein is an adverse prognostic factor for radiotherapy outcome in oropharyngeal carcinoma. Int J Radiat Oncol Biol Phys 2007;69:133–40CrossRefGoogle ScholarPubMed
36 Chugani, DC, Rome, LH, Kedersha, NL. Evidence that vault ribonucleoprotein particles localise to the nuclear pore complex. J Cell Sci 1993;106:23–9CrossRefGoogle Scholar
37 Gandara, DR, Lara, PNJ, Goldberg, Z, Le, QT, Mack, PC, Lau, DH et al. Tirapazamine: prototype for a novel class of therapeutic agents targeting tumour hypoxia. Semin Oncol 2002;29:102–9CrossRefGoogle Scholar
38 Henk, JM, Bishop, K, Shepherd, SF. Treatment of head and neck cancer with CHART and nimorazole: phase II study. Radiother Oncol 2003;66:65–70CrossRefGoogle ScholarPubMed