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    
Abstract/OtherAbstract:
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.
Authors:
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:  -    
Affiliation:
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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