Molecular and cytogenetic subgroups of oropharyngeal squamous cell carcinoma.
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.
Perrone
Federica
F
Unit of Experimental Molecular Pathology, Department of Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Italy.
Suardi
Simona
S
Pastore
Elisa
E
Casieri
Paola
P
Orsenigo
Marta
M
Caramuta
Stefano
S
Dagrada
Gianpaolo
G
Losa
Marco
M
Licitra
Lisa
L
Bossi
Paolo
P
Staurengo
Samantha
S
Oggionni
Maria
M
Locati
Laura
L
Cantu
Giulio
G
Squadrelli
Massimo
M
Carbone
Antonino
A
Pierotti
Marco A
MA
Pilotti
Silvana
S
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
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D019938:Cyclin D1; D066246:ErbB Receptors; D048493:Proto-Oncogene Proteins B-raf; D051358:Cyclin-Dependent Kinase 4