Document Detail

Validation of a Gene Expression Signature for Assessment of Lymph Node Metastasis in Oral Squamous Cell Carcinoma.
MedLine Citation:
PMID:  23045589     Owner:  NLM     Status:  Publisher    
PURPOSECurrent 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. METHODSA 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.ResultsThe 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%. CONCLUSIONCombining 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.
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 René Leemans; Ed Schuuring; Johannes A Langendijk; Martin Lacko; Maria J De Herdt; Jeroen C Jansen; Ruud H Brakenhoff; Piet J Slootweg; Robert P Takes; Frank C P Holstege
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-8
Journal Detail:
Title:  Journal of clinical oncology : official journal of the American Society of Clinical Oncology     Volume:  -     ISSN:  1527-7755     ISO Abbreviation:  J. Clin. Oncol.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8309333     Medline TA:  J Clin Oncol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Frank K.J. Leusink, Robert J.J. van Es, Paul J. van Diest, Sander R. van Hooff, and Frank C.P. Holstege, University Medical Center Utrecht, Utrecht; Paul Roepman, Agendia; Michiel W.M. van den Brekel, Marie-Louise F. van Velthuysen, Netherlands Cancer Institute; C. René Leemans and Ruud H. Brakenhoff, Vrije Universiteit Medical Center, Amsterdam; Robert P. Takes, Matthias A.W. Merkx, Piet J. Slootweg, Radboud University Nijmegen Medical Center, Nijmegen; Robert J. Baatenburg de Jong, Maria J. De Herdt, Erasmus Medical Center, Rotterdam; Martin Lacko and Ernst-Jan M. Speel, Maastricht University Medical Center, Maastricht; Ed Schuuring and Johannes A. Langendijk, University Medical Center Groningen, Groningen; J. Alain Kummer, Saint Antonius Hospital, Nieuwegein; and Jeroen C. Jansen, Leiden University Medical Center, Leiden, the Netherlands.
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