Molecular and cytogenetic subgroups of oropharyngeal squamous cell carcinoma
| Autor: | Maria Oggionni, Paola Casieri, Paolo Bossi, Marco Losa, Laura D. Locati, Samantha Staurengo, Giulio Cantù, Elisa Pastore, Marta Orsenigo, Antonino Carbone, Gianpaolo Dagrada, Marco A. Pierotti, Federica Perrone, Lisa Licitra, Simona Suardi, Massimo Squadrelli, Stefano Caramuta, Silvana Pilotti |
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| Přispěvatelé: | Perrone, Federica, Suardi, Simona, Pastore, Elisa, Casieri, Paola, Orsenigo, Marta, Caramuta, Stefano, Dagrada, Gianpaolo, Losa, Marco, Licitra, Lisa, Bossi, Paolo, Staurengo, Samantha, Oggionni, Maria, Locati, Laura, Cantu, Giulio, Squadrelli, Massimo, Carbone, Antonino, Pierotti, Marco A., Pilotti, Silvana |
| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Oropharyngeal Neoplasm
Proto-Oncogene Proteins B-raf medicine.medical_specialty Pathology Cancer Research Cell Cell Cycle Proteins Chromosome Aberration Cell Cycle Protein medicine Carcinoma Biomarkers Tumor Humans Cyclin D1 Genes Tumor Suppressor Epidermal growth factor receptor ErbB Receptor neoplasms Gene EGFR inhibitors Chromosome Aberrations Chromosome 7 (human) Human papillomavirus 16 biology Cytogenetics Cyclin-Dependent Kinase 4 Cytogenetic Analysi Cell cycle medicine.disease ErbB Receptors Oropharyngeal Neoplasms medicine.anatomical_structure Oncology Cytogenetic Analysis Cancer research biology.protein Carcinoma Squamous Cell Chromosomes Human Pair 9 Human |
| Popis: | Purpose: The aim of this study was to acquire further insights into the pathogenetic pathways of head and neck squamous cell carcinomas (HNSCC) that may be useful for identifying new biomarkers instrumental in developing more specific treatment approaches. Experimental Design: Cell cycle regulators and epidermal growth factor receptor (EGFR) and BRAF genes were analyzed in a series of 90 oropharyngeal SCCs of a cohort of surgically treated patients from a single institution, and the results were matched with the presence of high-risk human papillomavirus (HR-HPV) DNA and the TP53 status. Results: At least four distinct groups of tumors were identified sharing a common histology but displaying different molecular/cytogenetic patterns: (a) 19% were HPV-positive SCCs whose lack of alterations of the investigated genes could explain their particular natural history, which requires less aggressive treatment; (b) 37% were HPV-negative SCCs carrying TP53 mutations, which may be more effectively treated by drugs acting through p53-independent apoptosis; (c) 34% were HPV-negative SCCs carrying wild-type TP53 and loss of 9p21 (p16INK4a and p15INK4b) and/or cyclin D1 overexpression that justify treatment with DNA-damaging drugs followed by cell cycle inhibitors; and (d) 10% were HPV-negative lacking tumor suppressor genes and cell cycle alterations. The second, third, and fourth groups also showed an increased copy number of EGFR and chromosome 7 (43%) that might justify the additional or alternative use of EGFR inhibitors. Conclusions: Our findings suggest that assessing HPV, TP53, 9p21, and EGFR status may be crucial to finding more tailored and beneficial treatments for oropharyngeal SCCs. |
| Databáze: | OpenAIRE |
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