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Receptor tyrosine kinase profiles and human papillomavirus status in oropharyngeal squamous cell carcinoma
Author(s) -
Cortelazzi Barbara,
Verderio Paolo,
Ciniselli Chiara Maura,
Pizzamiglio Sara,
Bossi Paolo,
Gloghini Annunziata,
Gualeni Ambra V.,
Volpi Chiara C.,
Locati Laura,
Pierotti Marco A.,
Licitra Lisa,
Pilotti Silvana,
Perrone Federica
Publication year - 2015
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/jop.12301
Subject(s) - pten , cancer research , receptor tyrosine kinase , biology , tyrosine kinase , medicine , receptor , signal transduction , genetics , pi3k/akt/mtor pathway
Background Human papillomavirus ( HPV )‐positive and HPV ‐negative oropharyngeal squamous cell carcinomas ( OSCC s) are two distinct entities. We defined the molecular profiles of druggable receptor tyrosine kinases ( RTK s) in both groups. Materials and methods E5 expression and RTK alterations were studied in 17 HPV ‐positive and 59 HPV ‐negative formalin‐fixed OSCC s. RTK activation was explored in further 12 frozen OSCC s. Results The HPV ‐positive OSCC s showed E5 expression and 33.3% expressed low level of HER 2. The HPV ‐ negative OSCC s showed HER 2 expression (31.2%), increased HER 2 gene copy number (46.51%, P = 0.045) and HER 2 activation through HER 2/ EGFR heterodimerisation; HER 3 (51.06%, P = 0.008) and neuregulin (65.63%; P = 0.03) expression, HER 3 activation and HER 3/ EGFR heterodimerisation; and increased IGF ‐1R copy number (40.50%, P = 0.021), high IGF ‐1R cDNA values ( P = 0.002), IGF ‐1R activation and expression of IGF 1/2 and amphiregulin. PI 3 KCA mutations/expression/increased gene copy number and PTEN mutations were found in both groups, whereas PTEN gene loss was only observed in the HPV ‐positive cases. Conclusion Human papillomavirus‐positive and HPV ‐negative OSCC showed different RTK profiles. In HPV ‐positive cases, it would be interesting to study the expression of E5, which may modulate EGFR turnover and activate VEGF and PDGFR β. In HPV ‐negative cases, HER 3 may be a promising druggable biomarker that deserves further investigation. PI 3 KCA and PTEN alterations encourage the promising clinical evaluation of PI 3K/ mTOR inhibitor activity in OSCC , particularly in HPV ‐positive/ PI 3 KCA ‐mutated OSCC s because they may be driven by PI 3 KCA mutation alone.