Validation of a Gene Expression Signature for Assessment of Lymph Node Metastasis in Oral Squamous Cell Carcinoma

Sander R. van Hooff, Frank K. J. Leusink, Paul Roepman, Robert J. Baatenburg de Jong, Ernst-Jan M. Speel, Michiel W. M. van den Brekel, Marie-Louise F. van Velthuysen, Paul J. van Diest, Robert J. J. van Es, Matthias A. W. Merkx, J. Alain Kummer, C. Rene Leemans, Ed Schuuring, Johannes A. Langendijk, Martin Lacko, Maria J. De Herdt, Jeroen C. Jansen, Ruud H. Brakenhoff, Piet J. Slootweg, Robert P. TakesFrank C. P. Holstege*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Purpose Current assessment of lymph node metastasis in patients with head and neck squamous cell carcinoma is not accurate enough to prevent overtreatment. The aim of this study was validation of a gene expression signature for distinguishing metastasizing (N+) from nonmetastasizing (N0) squamous cell carcinoma of the oral cavity (OSCC) and oropharynx (OPSCC) in a large multicenter cohort, using a diagnostic DNA microarray in a Clinical Laboratory Improvement Amendments/International Organization for Standardization-approved laboratory. Methods A multigene signature, previously reported as predictive for the presence of lymph node metastases in OSCC and OPSCC, was first re-evaluated and trained on 94 samples using generic, whole-genome, DNA microarrays. Signature genes were then transferred to a dedicated diagnostic microarray using the same technology platform. Additional samples (n = 222) were collected from all head and neck oncologic centers in the Netherlands and analyzed with the diagnostic microarray. Human papillomavirus status was determined by real-time quantitative polymerase chain reaction. Results The negative predictive value (NPV) of the diagnostic signature on the entire validation cohort (n = 222) was 72%. The signature performed well on the most relevant subset of early-stage (cT1-T2N0) OSCC (n = 101), with an NPV of 89%. Conclusion Combining current clinical assessment with the expression signature would decrease the rate of undetected nodal metastases from 28% to 11% in early-stage OSCC. This should be sufficient to enable clinicians to refrain from elective neck treatment. A new clinical decision model that incorporates the expression signature is therefore proposed for testing in a prospective study, which could substantially improve treatment for this group of patients.
Original languageEnglish
Pages (from-to)4104-4110
JournalJournal of Clinical Oncology
Issue number33
Publication statusPublished - 20 Nov 2012

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