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Prognostic significance of cortactin levels in head and neck squamous cell carcinoma: comparison with epidermal growth factor receptor status.

Hofman P, Butori C, Havet K, Hofman V, Selva E, Guevara N, Santini J, Van Obberghen-Schilling E - Br. J. Cancer (2008)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Clinical and Experimental Pathology, Tissue Biobank Unit, Pasteur Hospital, Nice, and INSERM ERI-21, Faculty of Medicine, University of Nice-Sophia Antipolis, Nice, France. hofman.p@chu-nice.fr

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.

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Kaplan–Meier estimates of the 5-year local recurrence (A), disease-free survival (B), and overall survival (C), by cortactin status. Cortactin overexpressors had significantly lower disease-free and lower survival rates than nonoverexpressors. Additionally, cortactin overexpressors had higher local recurrence rates than nonoverexpressors. Kaplan–Meier estimates of the 5-year overall survival by both EGFR and cortactin status (D).
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fig3: Kaplan–Meier estimates of the 5-year local recurrence (A), disease-free survival (B), and overall survival (C), by cortactin status. Cortactin overexpressors had significantly lower disease-free and lower survival rates than nonoverexpressors. Additionally, cortactin overexpressors had higher local recurrence rates than nonoverexpressors. Kaplan–Meier estimates of the 5-year overall survival by both EGFR and cortactin status (D).

Mentions: The expression status of cortactin, as determined by immunohistochemistry, was evaluated for association with local recurrence using Kaplan–Meier survival analysis with log-rank statistics for determining significance. This analysis demonstrated that cortactin overexpression is associated with increased local recurrence rates. Patients with cortactin nonoverexpression have a local recurrence rate of 28%, compared with 49% for cortactin-overexpressing patients (Figure 3A). Among these latter patients with cortactin-overexpressing tumours, no differences relating to the initial treatment (postoperative radiotherapy alone or not, and postoperative chemotherapy plus radiotherapy or not) were noted. Univariate Cox analysis revealed a hazard ratio for cortactin overexpressors of 6.0 (P=0.014).


Prognostic significance of cortactin levels in head and neck squamous cell carcinoma: comparison with epidermal growth factor receptor status.

Hofman P, Butori C, Havet K, Hofman V, Selva E, Guevara N, Santini J, Van Obberghen-Schilling E - Br. J. Cancer (2008)

Kaplan–Meier estimates of the 5-year local recurrence (A), disease-free survival (B), and overall survival (C), by cortactin status. Cortactin overexpressors had significantly lower disease-free and lower survival rates than nonoverexpressors. Additionally, cortactin overexpressors had higher local recurrence rates than nonoverexpressors. Kaplan–Meier estimates of the 5-year overall survival by both EGFR and cortactin status (D).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2266845&req=5

fig3: Kaplan–Meier estimates of the 5-year local recurrence (A), disease-free survival (B), and overall survival (C), by cortactin status. Cortactin overexpressors had significantly lower disease-free and lower survival rates than nonoverexpressors. Additionally, cortactin overexpressors had higher local recurrence rates than nonoverexpressors. Kaplan–Meier estimates of the 5-year overall survival by both EGFR and cortactin status (D).
Mentions: The expression status of cortactin, as determined by immunohistochemistry, was evaluated for association with local recurrence using Kaplan–Meier survival analysis with log-rank statistics for determining significance. This analysis demonstrated that cortactin overexpression is associated with increased local recurrence rates. Patients with cortactin nonoverexpression have a local recurrence rate of 28%, compared with 49% for cortactin-overexpressing patients (Figure 3A). Among these latter patients with cortactin-overexpressing tumours, no differences relating to the initial treatment (postoperative radiotherapy alone or not, and postoperative chemotherapy plus radiotherapy or not) were noted. Univariate Cox analysis revealed a hazard ratio for cortactin overexpressors of 6.0 (P=0.014).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Clinical and Experimental Pathology, Tissue Biobank Unit, Pasteur Hospital, Nice, and INSERM ERI-21, Faculty of Medicine, University of Nice-Sophia Antipolis, Nice, France. hofman.p@chu-nice.fr

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.

Show MeSH
Related in: MedlinePlus