• Media type: E-Article
  • Title: Validation of a Gene Expression Signature for Assessment of Lymph Node Metastasis in Oral Squamous Cell Carcinoma
  • Contributor: van Hooff, Sander R.; Leusink, Frank K.J.; Roepman, Paul; Baatenburg de Jong, Robert J.; Speel, Ernst-Jan M.; van den Brekel, Michiel W.M.; van Velthuysen, Marie-Louise F.; van Diest, Paul J.; van Es, Robert J.J.; Merkx, Matthias A.W.; Kummer, J. Alain; Leemans, C. René; Schuuring, Ed; Langendijk, Johannes A.; Lacko, Martin; De Herdt, Maria J.; Jansen, Jeroen C.; Brakenhoff, Ruud H.; Slootweg, Piet J.; Takes, Robert P.; Holstege, Frank C.P.
  • imprint: American Society of Clinical Oncology (ASCO), 2012
  • Published in: Journal of Clinical Oncology
  • Language: English
  • DOI: 10.1200/jco.2011.40.4509
  • ISSN: 0732-183X; 1527-7755
  • Origination:
  • Footnote:
  • Description: <jats:sec><jats:title>Purpose</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> 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%. </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> 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. </jats:p></jats:sec>
  • Access State: Open Access