title: Immunohistochemical markers of distant metastasis in laryngeal and hypopharyngeal squamous cell carcinomas.
abstract: Metastasis remains a major cause of mortality in head and neck squamous cell carcinoma (HNSCC). Current clinicopathological features have shown limited predictability for the risk of distant metastasis in individual patients, and therefore more accurate and reliable markers are needed. The aim of this study was to investigate the ability of various molecular markers present in primary tumors to predict the risk of developing distant metastasis. Restrictive clinical criteria were applied for patient selection in order to carry out a case-control study with comparable clinical features on a group-wide basis and a similar risk of metastasis. All patients were surgically treated (with postoperative radiotherapy when appropriate) and classified as stage IV disease. Immunohistochemical analysis was performed for a panel of proteins known to participate in cellular processes relevant to metastatic dissemination (E-cadherin, annexin A2, cortactin, FAK, EGFR, p53, and p-AKT). Results showed that the loss of E-cadherin expression was significantly correlated with the risk of distant metastasis (P = 0.002; log-rank test), while the loss of annexin A2 expression was nearly statistically significant (P = 0.06). None of the other protein markers assessed were associated with the development of distant metastasis. Therefore, according to our data the loss of epithelial adhesion seems to play a central role in the development of metastasis in HNSCC, and more importantly, immunohistochemical assessment of key proteins involved in cell adhesion regulation, such as E-cadherin could represent a useful tool to evaluate easily and routinely the metastatic potential of these carcinomas.
authors.affiliation: Laboratorio 2 ORL, Department of Otolaryngology, Hospital Universitario Central de Asturias, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, 33006, Oviedo, Spain, juanpablo.rodrigo@sespa.princast.es.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Rodrigo
authors.forename: Patricia
authors.initials: P
authors.lastname: Martínez
authors.forename: Eva
authors.initials: E
authors.lastname: Allonca
authors.forename: Laura
authors.initials: L
authors.lastname: Alonso-Durán
authors.forename: Carlos
authors.initials: C
authors.lastname: Suárez
authors.forename: Aurora
authors.initials: A
authors.lastname: Astudillo
authors.forename: Juana María
authors.initials: JM
authors.lastname: García-Pedrero
mesh_terms: D017306:Annexin A2 / Q000235:genetics / Q000276:immunology; D014408:Biomarkers, Tumor / Q000276:immunology; D015820:Cadherins / Q000235:genetics / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology* / Q000532:radiotherapy / Q000601:surgery; D002448:Cell Adhesion / Q000235:genetics*; D003131:Combined Modality Therapy; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology* / Q000532:radiotherapy / Q000601:surgery; D007150:Immunohistochemistry; D007822:Laryngeal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology* / Q000532:radiotherapy / Q000601:surgery; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D009367:Neoplasm Staging; D046888:Tissue Array Analysis
chemical_list: C472822:ANXA2 protein, human; D017306:Annexin A2; D014408:Biomarkers, Tumor; D015820:Cadherins