Clinical relevance of copy number profiling in oral and oropharyngeal squamous cell carcinoma.

Pauline M W Van Kempen,Suvi Savola,Weibel W Braunius,Ronald Koole,Cathy B Moelans,Stefan M Willems,Robert J J Van Es,Widad Rifi,Wilko Grolman,Rob Noorlag

doi:10.1002/cam4.499

Abstract

Current conventional treatment modalities in head and neck squamous cell carcinoma (HNSCC) are nonselective and have shown to cause serious side effects. Unraveling the molecular profiles of head and neck cancer may enable promising clinical applications that pave the road for personalized cancer treatment. We examined copy number status in 36 common oncogenes and tumor suppressor genes in a cohort of 191 oropharyngeal squamous cell carcinomas (OPSCC) and 164 oral cavity squamous cell carcinomas (OSCC) using multiplex ligation probe amplification. Copy number status was correlated with human papillomavirus (HPV) status in OPSCC, with occult lymph node status in OSCC and with patient survival. The 11q13 region showed gain or amplifications in 59% of HPV-negative OPSCC, whereas this amplification was almost absent in HPV-positive OPSCC. Additionally, in clinically lymph node-negative OSCC (Stage I–II), gain of the 11q13 region was significantly correlated with occult lymph node metastases with a negative predictive value of 81%. Multivariate survival analysis revealed a significantly decreased disease-free survival in both HPV-negative and HPV-positive OPSCC with a gain of Wnt-induced secreted protein-1. Gain of CCND1 showed to be an independent predictor for worse survival in OSCC. These results show that copy number aberrations, mainly of the 11q13 region, may be important predictors and prognosticators which allow for stratifying patients for personalized treatment of HNSCC.

Highlights

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and is characterized by a biologically highly heterogeneous group of tumors
Archived formalin-fixed paraffin-embedded primary oropharyngeal squamous cell carcinomas (OPSCC) and oral cavity squamous cell carcinomas (OSCC) specimens were used for multiplex ligation-dependent probe amplification (MLPA)
In 28 cases, the quality or quantity of DNA was insufficient for MLPA analysis which resulted in the availability of copy number data for 355/383 (92%) tumors (191 OPSCC, 164 OSCC) from our initial study population

Summary

Introduction

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and is characterized by a biologically highly heterogeneous group of tumors. Treatment is predominantly based on location and TNM- classification and comprises mainly conventional methods such as surgery, radiotherapy, chemotherapy, or a combination of these. No treatment modalities exist that rely on the tumor-specific biology of HNSCC. Existing treatment modalities do not benefit patients and are often associated with (systemic) toxicities that reduce compliance and prevent timely completion of therapy [3]. Molecular profiling is an e ssential step toward an increased understanding of the pathogenic biology of HNSCC.

Methods

Results

Conclusion