Molecular differentiation of early and late stage laryngeal squamous cell carcinoma

Background: A current shortcoming in cancer prognostication and treatment is a lack of methods that adequately address the complexity and diversity of the disease. Prognostic marker systems based on single parameters have generally proven inadequate. Thus, multiparametric methods, which rely on many pieces of information, are ideally suited to the grouping of tumor subtypes and the identification of specific patterns of disease progression. Design: This study investigated, on an exploratory basis, whether genome wide alterations of loss and gain, using a panel of 122 gene probes (112 unique genes), discriminated between early stage (stage I and 2) and late stage (stage 3 and 4) laryngeal squamous cell carcinomas (LSCC). The LSCC cohort comprised 29 patients, 12 early and 17 late staged. Formalinfixed LSCC DNA was interrogated by a genome wide candidate gene panel (122 genes) using the multiplex ligation-dependent probe amplification assay. Results: Statistical analysis employed the nonparametric Wilcoxon 2-sample test. Significant differences between tumor stages of early versus late were seen for the following genes: ERBB4, CASP2, RECQL4, and BCL7A. Loss of ERBB4 (P = 0.045) and BCL7A (P = 0.019) significantly discriminated between early and late stage LSCC. Gain of RECQL4 copy number (P = 0.043) was associated with late LSCC. Gain of CASP2 (P = 0.043) marked early LSCC, whereas loss was associated with late LSCC. Conclusions: High-throughput genome wide approaches have the potential to yield discrete gene repertoires of early and late stage LSCC differentiation.