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Detection of MET oncogene/hepatocyte growth factor receptor in lymph node metastases from head and neck squamous cell
E Galeazzi1, M Olivero, F C Gervasio
1Department of Clinical Physiopathology, University of Turin School of Medicine, Italy.
Abstract:
The c-MET oncogene encodes the receptor for hepatocyte growth factor/scatter factor (HGF/SF), which is known to stimulate the invasive growth of epithelial cells cultured in vitro. The Met/HGF receptor is a heterodimeric transmembrane tyrosine kinase, which is a prototype for a new family of growth factor receptors. The c-MET oncogene is expressed in several types of epithelial tissue including keratinocytes and is over-expressed in a number of human carcinomas. Studies on various carcinoma cell lines have shown that over-expression and structural alteration of the receptor result in its activation and confer tumorigenesis. We have studied Met/HGF receptor expression in tissue specimens from 34 patients with head and neck squamous cell carcinomas (HNSCC) and in 17 regional lymph node metastases. Western blot analysis was employed, using monoclonal antibodies directed against either the intracellular or extracellular domain of the receptor. Each sample was compared to its normal counterpart. The receptor did not show any major structural alterations in HNSCC tissues, but its expression was increased from 2- to 50-fold in about 70% of tumors. Immunohistochemistry then showed that the same antibodies stained only a few cells in the basal layer of normal squamous epithelium but intensely marked tumor cells. In the lymph node metastases of Met-positive tumors, receptor expression was maintained and sometimes increased with respect to primary tumors. Immunohistochemical analysis of the metastatic lymph nodes showed that cells were negative in the normal lymphatic tissue and strongly stained in tumor cells. Over-expression of the Met/HGF receptor was found at all tumor stages but was more significant in those associated with enlarged or multiple (N2-N3) lymph node metastases. These data show that expression of the Met/HGF receptor may be involved in the progression of HNSCC towards a metastatic phenotype and may be a useful marker of head and neck tumor cell spread to regional lymph nodes.
Insights
The Met/HGF receptor is overexpressed in most head and neck squamous cell carcinomas (HNSCC), correlating with increased lymph node metastasis. This suggests Met/HGF receptor expression is a potential marker for HNSCC spread.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- The c-MET oncogene encodes the Met/HGF receptor, a tyrosine kinase implicated in epithelial cell invasion.
- Met/HGF receptor overexpression is observed in various human carcinomas, contributing to tumorigenesis.
- Head and neck squamous cell carcinoma (HNSCC) is a significant malignancy where understanding receptor involvement is crucial.
Purpose of the Study:
- To investigate Met/HGF receptor expression in HNSCC tissues and regional lymph node metastases.
- To determine if Met/HGF receptor expression correlates with tumor stage and metastatic potential.
- To evaluate Met/HGF receptor as a potential biomarker for HNSCC progression.
Main Methods:
- Western blot analysis of Met/HGF receptor expression in 34 HNSCC patient specimens and 17 lymph node metastases compared to normal counterparts.
- Immunohistochemistry using monoclonal antibodies against Met/HGF receptor to localize expression in tumor and normal tissues.
- Correlation analysis between Met/HGF receptor expression levels and clinicopathological features, including lymph node metastasis status (N2-N3).
Main Results:
- Met/HGF receptor expression was increased 2- to 50-fold in approximately 70% of HNSCC tumors compared to normal tissue.
- Immunohistochemistry revealed intense Met/HGF receptor staining in tumor cells, contrasting with minimal staining in normal squamous epithelium.
- Receptor expression was maintained or increased in lymph node metastases, with higher expression correlating significantly with advanced lymph node involvement (N2-N3).
Conclusions:
- Met/HGF receptor is frequently overexpressed in HNSCC.
- Overexpression of the Met/HGF receptor is associated with the metastatic progression of HNSCC.
- Met/HGF receptor expression may serve as a valuable biomarker for detecting head and neck tumor cell spread to regional lymph nodes.