MUC4(sialomucin complex) expression in salivary tumors and SCC of the upper aerodigestive tract

Abstract

Chromosome l lq13 amplification has been found frequently in head and neck squamous cell carcinomas (HNSCCs), indicating poor prognosis. The EMS1 gene has been identified as one of the "active" oncogenes in this region because it is overexpressed in all carcinomas with EMS1 amplification, and this overexpression causes increased cell motility and invasion in vitro. However, little is known about the prognostic significance of individual EMS 1 amplification in HNSCC. Our objective was to further address the frequency of EMS 1 amplification in HNSCC and to evaluate its correlation with clinicopathologic variables, relapse, and survival. Methods: Tissue samples from 104 consecutive patients with primary HNSCC who underwent surgical resection of their tumors were studied. After DNA extraction, the EMS 1 copy number in tumor samples was estimated with the polymerase chain reaction method. The presence or absence of amplification was correlated with the anatomic site, T stage, nodal involvement, pathologic grade, disease recurrence, distant metastasis, clinical outcome (disease status), and survival. Patients were observed for at least 36 months (mean followup 54 months). Results: EMS1 amplification was identified in 21 cases (20%). Amplification was related with advanced T stages (P = 0.003), lymph node involvement (P = 0.02), and poor histologic differentiation (P = 0.018). Recurrent disease was identiffed in 76% (16/21) of cases with amplification and 39% (32/83) of cases without amplification (P = 0.006). Seventeen patients (81%) with EMS1 amplification and 35 patients (42%) without amplification died of disease (P = 0.003). EMS1 amplification status, individually, had a significant effect on survival (the 3-year survival was 54% in nonamplifled cases and 7% in amplified cases, P < 0.0001). In multivariate analysis (Cox regression model), EMS1 amplification was found to be an independent predictor of mortality by the tumor (P = 0.003). Conclusion: Amplification of the EMS1 gene seems to be an important biological marker indicating poor prognosis in HNSCC, independent of clinical stage, histologic differentiation, or anatomic site. This may confirm its role as an "active" oncogene in the llq13 region.