title: Molecular and cytogenetic subgroups of oropharyngeal squamous cell carcinoma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Unit of Experimental Molecular Pathology, Department of Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Perrone
authors.forename: Simona
authors.initials: S
authors.lastname: Suardi
authors.forename: Elisa
authors.initials: E
authors.lastname: Pastore
authors.forename: Paola
authors.initials: P
authors.lastname: Casieri
authors.forename: Marta
authors.initials: M
authors.lastname: Orsenigo
authors.forename: Stefano
authors.initials: S
authors.lastname: Caramuta
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Dagrada
authors.forename: Marco
authors.initials: M
authors.lastname: Losa
authors.forename: Lisa
authors.initials: L
authors.lastname: Licitra
authors.forename: Paolo
authors.initials: P
authors.lastname: Bossi
authors.forename: Samantha
authors.initials: S
authors.lastname: Staurengo
authors.forename: Maria
authors.initials: M
authors.lastname: Oggionni
authors.forename: Laura
authors.initials: L
authors.lastname: Locati
authors.forename: Giulio
authors.initials: G
authors.lastname: Cantu
authors.forename: Massimo
authors.initials: M
authors.lastname: Squadrelli
authors.forename: Antonino
authors.initials: A
authors.lastname: Carbone
authors.forename: Marco A
authors.initials: MA
authors.lastname: Pierotti
authors.forename: Silvana
authors.initials: S
authors.lastname: Pilotti
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000145:classification* / Q000235:genetics* / Q000821:virology; D018797:Cell Cycle Proteins / Q000502:physiology; D002869:Chromosome Aberrations; D002899:Chromosomes, Human, Pair 9; D019938:Cyclin D1 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D020732:Cytogenetic Analysis; D066246:ErbB Receptors / Q000378:metabolism; D016147:Genes, Tumor Suppressor / Q000502:physiology; D052162:Human papillomavirus 16 / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D009959:Oropharyngeal Neoplasms / Q000145:classification* / Q000235:genetics* / Q000821:virology; D048493:Proto-Oncogene Proteins B-raf / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D019938:Cyclin D1; D066246:ErbB Receptors; D048493:Proto-Oncogene Proteins B-raf; D051358:Cyclin-Dependent Kinase 4