title: Staging of head and neck squamous cell carcinoma using the MET oncogene product as marker of tumor cells in lymph node metastases.
abstract: In head and neck squamous cell carcinomas (HNSCC), metastasis to cervical lymph nodes is a major determinant of patient outcome. To detect metastases, we used the MET oncogene as marker, which encodes the receptor for hepatocyte growth factor/scatter factor, mediating epithelial cell motility and invasiveness. The MET gene is expressed in epithelia and over-expressed in carcinomas of specific histotypes, but not in lymphatic tissue. A total of 151 lymph nodes from 20 squamous cell carcinomas were studied with both in-depth histology and end-point and real-time quantitative RT-PCR. MET-encoded sequences were found in 61 of 151 nodes (40%), of which 24 (16%) were found metastatic by in-depth histopathology. Parallel routine histopathologic analysis of 654 lymph nodes from the same cases identified 36 metastases (5%). Real-time quantitative RT-PCR was used to measure MET gene-specific mRNA in normal tissues, primary tumors and lymphatic metastases and showed a 2-8-fold increased expression in tumor cells which metastasize. RT-PCR for 3 cytokeratins expressed in HNSCC (K4, K10 and K13) proved to be less sensitive in detecting occult lymphatic metastases. Western blot analysis demonstrated the presence of the full-size MET receptor in primary tumors and lymph node metastases; immunohistochemistry showed receptor localization in tumor cells. Altogether, these data demonstrate that the MET gene product is a valuable marker with which to detect occult tumor cells in lymph nodes, thanks to its high expression in metastatic cells. After RT-PCR analysis we were able to attribute a more advanced stage to 10 out of 20 HNSCC cases, including 5 cases classified as tumor-free after routine histopathology.
authors.affiliation: Department of Clinical Physiopathology, University of Torino School of Medicine, Torino, Italy. mfdirenzo@ircc.unito.it
authors.forename: G
authors.initials: G
authors.lastname: Cortesina
authors.forename: T
authors.initials: T
authors.lastname: Martone
authors.forename: E
authors.initials: E
authors.lastname: Galeazzi
authors.forename: M
authors.initials: M
authors.lastname: Olivero
authors.forename: A
authors.initials: A
authors.lastname: De Stefani
authors.forename: M
authors.initials: M
authors.lastname: Bussi
authors.forename: G
authors.initials: G
authors.lastname: Valente
authors.forename: P M
authors.initials: PM
authors.lastname: Comoglio
authors.forename: M F
authors.initials: MF
authors.lastname: Di Renzo
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004848:Epithelium / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D009055:Mouth / Q000378:metabolism; D009154:Mutation; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D019859:Proto-Oncogene Proteins c-met