Molecular signatures associated with clinical outcome in patients with high-risk head-and-neck squamous cell carcinoma treated by surgery and radiation

Purpose: The local-regional control rate for advanced head-and-neck squamous cell carcinoma (HNSCC) remains poor and is unpredictable for a given individual. This study examined whether gene expression patterns developed from tumors from surgicopathologic, criteria-defined, high-risk HNSCC patients could be correlated with clinical outcomes, namely, metastasis or nonrecurrent disease. Methods and Materials: Fifteen primary tumors from patients treated with a consistent protocol of surgery followed by radiotherapy were examined. Seven of these tumors were from high-risk patients who developed distant metastasis (DM), and eight tumors were from patients with no recurrence (NR) (median follow-up, 59 months). Results: Unsupervised clustering of gene expression did not separate the two groups from one another, but when supervised methodologies were applied, 205 genes discriminated the two groups. Within the DM group, genes associated with cell growth and proliferation; DNA replication, recombination, and repair; antiapoptotic pathways; cell adhesion; and angiogenesis were identified. For NR samples, discriminatory genes were associated with the onset of apoptosis. Conclusions: Our data suggest that gene expression analysis of surgically excised HNSCC tumors from patients considered at high risk for recurrence has the potential to identify individuals susceptible to metastasis on the basis of distinct gene-expression patterns. These patients would be ideal candidates for testing systemic therapy.