1. ¹Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice, France
2. ²INSERM ERI-21, Faculty of Medicine, University of Nice – Sophia Antipolis, Nice, France
3. ³Tissue Biobank Unit, Pasteur Hospital, Nice, France
4. ⁴Department of Oto-Rhino-Laryngology, Pasteur Hospital, Nice, France
5. ⁵Institute of Signaling, Developmental Biology and Cancer Research UMR CNRS 6543, Centre Antoine Lacassagne, Nice, France

Correspondence: Dr E Van Obberghen-Schilling, Institute of Signaling, Developmental Biology and Cancer Research UMR CNRS 6543, Centre Antoine Lacassagne, 33 Avenue de Valombrose, Nice 06189, France; E-mail: vanobber@unice.fr; Professor P Hofman, INSERM ERI-21, Faculty of Medicine, Avenue de Valombrose, Nice 06107, France; E-mail: hofman.p@chu-nice.fr

⁶These authors contributed equally to this work.

Received 30 October 2007; Revised 9 January 2008; Accepted 14 January 2008; Published online 12 February 2008.

Abstract

Cortactin is an actin-binding Src substrate involved in cell motility and invasion. In this study, we sought to examine the prognostic importance of cortactin protein expression in head and neck squamous cell carcinoma (HNSCC). To do so, cortactin and EGF receptor (EGFR) expression was retrospectively evaluated by immunohistochemistry in a tissue microarray composed of 176 HNSCCs with a mean follow-up time of 5 years. Cortactin immunoreactivity was weak to absent in normal epithelial tissue. Overexpression of the protein in 77 out of 176 tumours (44%) was associated with more advanced tumour-node-metastasis stage and higher histologic grade. Cortactin overexpression was associated with significantly increased local recurrence rates (49 vs 28% for high and low expressing carcinomas, respectively), decreased disease-free survival (17 vs 61%), and decreased the 5-year overall survival of (21 vs 58%), independently of the EGFR status. In multivariate analysis, cortactin expression status remained an independent prognostic factor for local recurrence, disease-free survival, and overall survival. Importantly, we identified a subset of patients with cortactin-overexpressing tumours that displayed low EGFR levels and a survival rate that equalled that of patients with tumoral overexpression of both EGFR and cortactin. These findings identify cortactin as a relevant prognostic marker and may have implications for targeted therapies in patients with HNSCC.