title: Copy number gain of PIK3CA and MET is associated with poor prognosis in head and neck squamous cell carcinoma.
abstract: The incidence of head and neck squamous cell carcinomas is still growing, and the long-term prognosis of advanced disease remains poor. Only a fraction of head and neck cancers are sensitive to the EGFR-inhibitor cetuximab, which is the only registered targeted therapy available today. In several cancers, gene copy number alterations of MET and PIK3CA have been found to be prognostic and predictive for therapy response. The aim of this study was to systematically analyze in head and neck cancers the pathological characteristics and prognostic significance of copy number changes of MET and PIK3CA genes. MET and PIK3CA copy numbers were analyzed by fluorescence in situ hybridization in tumor samples of 152 patients. Expression of EGFR, p16, and Ki67 was studied by immunohistochemistry. High polysomy of PIK3CA (chromosome 3) was found in 20 % of cases and amplification in 4.5 %. Regarding MET, 35 % of cases showed low or high polysomy of the gene (chromosome 7), while no intra-chromosomal amplification of MET was detected. PIK3CA copy number gain (high polysomy or amplification) was significantly associated with shorter disease-specific survival, larger tumor volume, and lower p16 expression. MET copy number gain (low or high polysomy) in tumors was significantly associated with shorter disease-specific survival and lower level of EGFR. PIK3CA and MET may play an important role in oncogenesis of certain specific subtypes of head and neck cancer. There is an urgent need for the development of novel targeted therapies against these tumors associated with poor prognosis.
authors.affiliation: MTA-SE Pathobiochemistry Research Group, 1094, Budapest, Tűzoltó Str. 37-47, Hungary. brauswetter.diana@med.semmelweis-univ.hu.
authors.forename: Diána
authors.initials: D
authors.lastname: Brauswetter
authors.affiliation: Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Semmelweis University, 1083, Budapest, Szigony Str. 36, Hungary.
authors.forename: Kornél
authors.initials: K
authors.lastname: Dános
authors.affiliation: MTA-SE Pathobiochemistry Research Group, 1094, Budapest, Tűzoltó Str. 37-47, Hungary.
authors.forename: Bianka
authors.initials: B
authors.lastname: Gurbi
authors.affiliation: MTA-SE Pathobiochemistry Research Group, 1094, Budapest, Tűzoltó Str. 37-47, Hungary.
authors.forename: Éva Fruzsina
authors.initials: ÉF
authors.lastname: Félegyházi
authors.affiliation: Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Semmelweis University, 1083, Budapest, Szigony Str. 36, Hungary.
authors.forename: Ede
authors.initials: E
authors.lastname: Birtalan
authors.affiliation: Department of Pathology and Experimental Cancer Research, Semmelweis University, 1085, Budapest, Üllői Str. 26, Hungary.
authors.forename: Nóra
authors.initials: N
authors.lastname: Meggyesházi
authors.affiliation: Department of Pathology and Experimental Cancer Research, Semmelweis University, 1085, Budapest, Üllői Str. 26, Hungary.|MTA-SE Tumor Progression Research Group, 1085, Budapest, Üllői Str. 26, Hungary.
authors.forename: Tibor
authors.initials: T
authors.lastname: Krenács
authors.affiliation: Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Semmelweis University, 1083, Budapest, Szigony Str. 36, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Tamás
authors.affiliation: MTA-SE Pathobiochemistry Research Group, 1094, Budapest, Tűzoltó Str. 37-47, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Peták
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D058534:Class I Phosphatidylinositol 3-Kinases; D005260:Female; D005784:Gene Amplification / Q000235:genetics; D018628:Gene Dosage; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008297:Male; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: CNG (copy number gain); Head and neck cancer (HNC); MET; PIK3CA
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