Limits...
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.In multivariate analysis, cortactin expression status remained an independent prognostic factor for local recurrence, disease-free survival, and overall survival.

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

Cortactin expression in normal oral mucosa and HNSCC. Staining of cortactin was performed as indicated in Materials and Methods. Normal epithelium (A–B) is devoid of staining, arrowheads indicate cortactin staining of blood vessels. Scale bar represents 200 μm in the tissue core shown in panel A and 100 μm in the higher magnification images shown in panels B–F. (C–D) Squamous cell carcinoma demonstrating strong membrane and cytoplasmic staining, respectively. (E) Squamous cell carcinoma exhibiting weak staining. (F) Squamous cell carcinoma displaying absence of immunohistochemical staining. Only strong staining (C–D) was scored as cortactin overexpression. Weak staining or absence of staining (E–F) was scored as negative for this study. Calibration bar represents 200 μm in images on the left.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2266845&req=5

fig1: Cortactin expression in normal oral mucosa and HNSCC. Staining of cortactin was performed as indicated in Materials and Methods. Normal epithelium (A–B) is devoid of staining, arrowheads indicate cortactin staining of blood vessels. Scale bar represents 200 μm in the tissue core shown in panel A and 100 μm in the higher magnification images shown in panels B–F. (C–D) Squamous cell carcinoma demonstrating strong membrane and cytoplasmic staining, respectively. (E) Squamous cell carcinoma exhibiting weak staining. (F) Squamous cell carcinoma displaying absence of immunohistochemical staining. Only strong staining (C–D) was scored as cortactin overexpression. Weak staining or absence of staining (E–F) was scored as negative for this study. Calibration bar represents 200 μm in images on the left.

Mentions: Cortactin immunoreactivity in normal epithelial tissue was low to undetectable (Figure 1A–B). Staining was observed in blood vessels of the underlying connective tissue, both in capillary endothelial cells and in α-actin-positive smooth muscle cells of larger vessels. Interestingly, the presence of cortactin in endothelial cells and in perivascular cells was often mutually excusive (data not shown). Epidermal growth factor receptor staining in normal epithelium was intense in the basal and suprabasal proliferative layers and undetectable in the connective tissue and blood vessels (not shown).


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)

Cortactin expression in normal oral mucosa and HNSCC. Staining of cortactin was performed as indicated in Materials and Methods. Normal epithelium (A–B) is devoid of staining, arrowheads indicate cortactin staining of blood vessels. Scale bar represents 200 μm in the tissue core shown in panel A and 100 μm in the higher magnification images shown in panels B–F. (C–D) Squamous cell carcinoma demonstrating strong membrane and cytoplasmic staining, respectively. (E) Squamous cell carcinoma exhibiting weak staining. (F) Squamous cell carcinoma displaying absence of immunohistochemical staining. Only strong staining (C–D) was scored as cortactin overexpression. Weak staining or absence of staining (E–F) was scored as negative for this study. Calibration bar represents 200 μm in images on the left.
© Copyright Policy
Related In: Results  -  Collection

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

fig1: Cortactin expression in normal oral mucosa and HNSCC. Staining of cortactin was performed as indicated in Materials and Methods. Normal epithelium (A–B) is devoid of staining, arrowheads indicate cortactin staining of blood vessels. Scale bar represents 200 μm in the tissue core shown in panel A and 100 μm in the higher magnification images shown in panels B–F. (C–D) Squamous cell carcinoma demonstrating strong membrane and cytoplasmic staining, respectively. (E) Squamous cell carcinoma exhibiting weak staining. (F) Squamous cell carcinoma displaying absence of immunohistochemical staining. Only strong staining (C–D) was scored as cortactin overexpression. Weak staining or absence of staining (E–F) was scored as negative for this study. Calibration bar represents 200 μm in images on the left.
Mentions: Cortactin immunoreactivity in normal epithelial tissue was low to undetectable (Figure 1A–B). Staining was observed in blood vessels of the underlying connective tissue, both in capillary endothelial cells and in α-actin-positive smooth muscle cells of larger vessels. Interestingly, the presence of cortactin in endothelial cells and in perivascular cells was often mutually excusive (data not shown). Epidermal growth factor receptor staining in normal epithelium was intense in the basal and suprabasal proliferative layers and undetectable in the connective tissue and blood vessels (not shown).

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.In multivariate analysis, cortactin expression status remained an independent prognostic factor for local recurrence, disease-free survival, and overall survival.

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