Background. RAS gene mutations have an impact on treatment response and overall prognosis for certain types of cancer. Objectives. To determine the prevalence and impact of K-RAS codons 12 and 13 mutations in patients with locally advanced HNSCC treated with primary or adjuvant chemo-radiation. Methods. 428 consecutive patients were treated with chemo-radiation therapy and followed for a median of 37 months. From these, 199 paraffin embedded biopsy or surgical specimens were retrieved. DNA was isolated and analyzed for K-RAS mutational status. Results. DNA extraction was successful in 197 samples. Of the 197 specimens, 3.5% presented K-RAS codon 12 mutations. For mutated cases and non-mutated cases, complete initial response to chemoradiation therapy was 71 and 73% ( ). LRC was respectively 32 and 83% ( ), DFS was 27 and 68% ( ), distant metastasis-free survival was 100 and 81% ( ) and OS was 57 and 65% ( ) at three years. K-Ras codon 13 analysis revealed no mutation. Conclusion. K-RAS codon 12 mutational status, although not associated with a difference in response rate, may influence the failure pattern and the type of therapy offered to patients with HNSCC. Our study did not reveal any mutation of K-RAS codon 13. 1. Introduction Head and neck squamous cell carcinoma (HNSCC) accounts for 47？000 new malignancies diagnosed each year in the USA and is the sixth most common human neoplasm, representing about 3% of all cancers [1]. Despite efforts to improve conventional treatment, survival rates for these cancers have not changed significantly over the past decade. Initial evaluation of patients includes clinical assessment, study of tumor histological characteristics and tumor grading, as well as local-regional and distant metastasis status. Traditional clinical, radiological, and histopathological characteristics are however limited in their ability to accurately predict response to treatment. This has motivated many researchers to identify molecular characteristics that may influence overall prognosis. A recent interest in molecular biology and genetics is motivated by the belief that understanding the origins of cancer can lead to more logical means of treating malignancies [2]. Identification of molecular events that lead to HNSCC may represent a key to predicting biological behaviour and may consequently lead to new treatment modalities that could lead to increases in survival rates. [3, 4]. Despite the recent progress in the field of molecular biology, clinicians need more tools to predict response to therapy or to identify patients at high risk of
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