Data from CD44 Expression Predicts Local Recurrence after Radiotherapy in Larynx Cancer

Abstract

Abstract Purpose: To find molecular markers from expression profiling data to predict recurrence of laryngeal cancer after radiotherapy. Experimental Design: We generated gene expression data on pre-treatment biopsies from 52 larynx cancer patients. Patients developing a local recurrence were matched for T-stage, subsite, treatment, gender and age with non-recurrence patients. Candidate genes were then tested by immunohistochemistry on tumor material from a second series of 76 patients. Both series comprised early stage cancer treated with radiotherapy alone. Finally, gene expression data of eight larynx cancer cell lines with known radiosensitivity were analyzed. Results: Nineteen patients with a local recurrence were matched with 33 controls. Gene sets for hypoxia, proliferation and intrinsic radiosensitivity did not correlate with recurrence, whereas expression of the putative stem cell marker CD44 did. In a supervised analysis, probes for all three splice variants of CD44 on the array appeared in the top 10 most significantly correlated with local recurrence. Immunohistochemical analysis of CD44 expression on the independent validation series confirmed CD44's predictive potential. In 8 larynx cancer cell lines, CD44 gene expression did not correlate with intrinsic radiosensitivity although it did correlate significantly with plating efficiency, consistent with a relationship with stem cell content. Conclusions: CD44 was the only biological factor tested which significantly correlated with response to radiotherapy in early stage larynx cancer patients, both at the mRNA and protein levels. Further studies are needed to confirm this and to assess how general these findings are for other head and neck tumor stages and sites. Clin Cancer Res; 16(21); 5329–38. ©2010 AACR.

Authors 18

1. Monique C. de Jong
   Affiliation as printed

   Experimental Therapy,

   Radiation Oncology,

2. Jimmy Pramana
   Affiliation as printed

   Experimental Therapy,

   Head and Neck Surgery and

3. Jacqueline E. van der Wal

   The Netherlands Cancer Institute

   Affiliation as printed

   Department of Experimental Therapy, The Netherlands Cancer Institute, The Netherlands

   Departments of

4. Martin Lacko
   Affiliation as printed

   Otorhinolaryngology and Head and Neck Surgery,

5. Carine J. Peutz‐Kootstra
   Affiliation as printed

   Pathology and

6. Jos M. de Jong

   Maastricht University Medical Centre

   Affiliation as printed

   Radiation Oncology, University Medical Center Maastricht, The Netherlands; Departments of

7. Robert Paul Takes
   Affiliation as printed

   Otorhinolaryngology and Head and Neck Surgery and

8. Johannes H. A. M. Kaanders

   University Medical Center Groningen · Radboud University Nijmegen · University of Groningen · Radboud University Medical Center

   Affiliation as printed

   Departments of 10 Pathology and 11 Otorhinolaryngology and Head and Neck Surgery, University Medical Center Groningen, University of Groningen, The Netherlands;

   Radiation Oncology, Radboud University Medical Centre Nijmegen, The Netherlands;

9. Bernard F. A. M. van der Laan

   The Netherlands Cancer Institute

   Affiliation as printed

   Department of Experimental Therapy, The Netherlands Cancer Institute, The Netherlands

   Departments of

10. Jasper E. Wachters

    The Netherlands Cancer Institute

    Affiliation as printed

    Department of Experimental Therapy, The Netherlands Cancer Institute, The Netherlands

    Departments of

11. Jeroen C. Jansen Aachen Department of Otorhinolaryngology and Head & Neck Surgery

    Leiden University Medical Center

    Affiliation as printed

    Department of Otorhinolaryngology and Head and Neck Surgery, Leiden University Medical Center, The Netherlands;

12. Coen R. N. Rasch
    Affiliation as printed

    Radiation Oncology,

13. Marie‐Louise F. van Velthuysen

    The Netherlands Cancer Institute

    Affiliation as printed

    Pathology, The Netherlands Cancer Institute, The Netherlands; Departments of

14. Reidar A. Grenman

    University of Turku

    Affiliation as printed

    Department of Otorhinolaryngology -Head and Neck Surgery and Medical Biochemistry, University of Turku, Finland

15. Frank J P Hoebers
    Affiliation as printed

    Radiation Oncology,

16. Ed M. D. Schuuring

    The Netherlands Cancer Institute

    Affiliation as printed

    Department of Experimental Therapy, The Netherlands Cancer Institute, The Netherlands

    Departments of

17. Michiel W. M. van den Brekel
    Affiliation as printed

    Head and Neck Surgery and

18. Adrian C. Begg corresponding
    Affiliation as printed

    Experimental Therapy,