TY - JOUR
T1 - Validation of a Gene Expression Signature for Assessment of Lymph Node Metastasis in Oral Squamous Cell Carcinoma
AU - van Hooff, Sander R.
AU - Leusink, Frank K. J.
AU - Roepman, Paul
AU - de Jong, Robert J. Baatenburg
AU - Speel, Ernst-Jan M.
AU - van den Brekel, Michiel W. M.
AU - van Velthuysen, Marie-Louise F.
AU - van Diest, Paul J.
AU - van Es, Robert J. J.
AU - Merkx, Matthias A. W.
AU - Kummer, J. Alain
AU - Leemans, C. Rene
AU - Schuuring, Ed
AU - Langendijk, Johannes A.
AU - Lacko, Martin
AU - De Herdt, Maria J.
AU - Jansen, Jeroen C.
AU - Brakenhoff, Ruud H.
AU - Slootweg, Piet J.
AU - Takes, Robert P.
AU - Holstege, Frank C. P.
PY - 2012/11/20
Y1 - 2012/11/20
N2 - 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.
AB - 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.
KW - CLINICALLY NEGATIVE NECK
KW - HUMAN-PAPILLOMAVIRUS
KW - MOLECULAR CLASSIFICATION
KW - OROPHARYNGEAL CANCER
KW - HEAD
KW - MANAGEMENT
KW - PATTERNS
KW - BIOPSY
KW - TRIAL
U2 - 10.1200/JCO.2011.40.4509
DO - 10.1200/JCO.2011.40.4509
M3 - Article
C2 - 23045589
VL - 30
SP - 4104
EP - 4110
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 33
ER -