Objectives: The band 4.1 (FERM) proteins, normally adjacent to the cytoplasmic membrane, are part of the molecular scaffolding involved in filamentous actin–based signaling modules. Another FERM protein, NF2 (merlin), has known tumor-suppressor activity. We have previously shown that FERM up-regulation is one of many changes seen in tumor progression. Here, our objective was to validate this by immunohistochemical analysis (IHC) and tissue microarrays (TMAs) in a new prospective cohort. Design: We constructed TMAs from patient tissue; IHC was performed with antibodies against ezrin, moesin, merlin, and willin, a newly described FERM protein. Patients: Fifty-six consenting patients with primary upper aerodigestive tract squamous cell carcinoma (SCC). Results: Mean ± SD cytoplasmic staining in primary SCC was highest for ezrin (1.7 ± 0.8) vs moesin (1.0 ± 0.9), merlin (1.2 ± 0.6), and willin (1.3 ± 0.8). Likewise, ezrin membranous staining was strongest (1.1 ± 1.1) vs moesin (0.3 ± 0.7), merlin (0.1 ± 0.4), and willin (0.6 ± 0.9). Only merlin and willin had nuclear localization. Sixteen patients developed locoregional recurrence (LRR) (median, 10 months). Strong tumor ezrin cytoplasmic localization was predictive of LRR (P = .02, log-rank test). Cytoplasmic tumor moesin expression was also predictive of LRR (P = .04, log-rank test). Conclusions: Our results confirm our previous pilot data and the reports of others indicating that strong cytoplasmic mislocalization of ezrin and moesin in SCC may be predictive of LRR, and thus these markers have potential as predictive biomarkers. We continue to accrue patients and follow-up time in this study.
Archives of Otolaryngology - Head & Neck Surgery – American Medical Association
Published: Aug 1, 2006
Keywords: biological markers,cytoplasm,tissue microarray