Research
Membranous expression of Her3 is associated with a decreased survival in head and neck squamous cell carcinoma
-
* Corresponding author: Stephen M Hewitt genejock@helix.nih.gov
- † Equal contributors
1 Tissue Array Research Program, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
2 Applied Molecular Pathology Laboratory, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
3 Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA
4 Department of Pathology, University of Virginia Health System, Charlottesville, VA 22908, USA
Journal of Translational Medicine 2011, 9:126 doi:10.1186/1479-5876-9-126
Published: 29 July 2011Abstract
Background
Head and neck squamous cell carcinoma (HNSCC) still remains a lethal malignancy benefiting from the identification of the new target for early detection and/or development of new therapeutic regimens based on a better understanding of the biological mechanism for treatment. The overexpression of Her2 and Her3 receptors have been identified in various solid tumors, but its prognostic relevance in HNSCC remains controversial.
Methods
Three hundred eighty-seven primary HNSCCs, 20 matching metasis and 17 recurrent HNSCCs were arrayed into tissue microarrays. The relationships between Her2 and Her3 protein expression and clinicopathological parameters/survival of HNSCC patients were analyzed with immunohistochemistry.
Results
Her3 is detected as either a cytoplasmic or a membranous dominant expression pattern whereas Her2 expression showed uniform membranous form. In primary tumor tissues, high membranous Her2 expression level was found in 104 (26.9%) cases while positive membranous and cytoplasmic Her3 expression was observed in 34 (8.8%) and 300 (77.5%) samples, respectively. Membranous Her2 expression was significantly associated with histological grade (P = 0.021), as grade 2 tumors showed the highest positive expression. Membranous Her3 over-expression was significantly prevalent in metastatic tissues compared to primary tumors (P = 0.003). Survival analysis indicates that membranous Her3 expression is significantly associated with worse overall survival (P = 0.027) and is an independent prognostic factor in multivariate analysis (hazard ratio, 1.51; 95% confidence interval, 1.01-2.23; P = 0.040).
Conclusions
These results suggest that membranous Her3 expression is strongly associated with poor prognosis of patients with HNSCC and is a potential candidate molecule for targeted therapy.