title: Copy number gain of 11q13.3 genes associates with pathological stage in hypopharyngeal squamous cell carcinoma.
abstract: Squamous cell carcinomas of the hypopharynx (HPSCC) and oropharynx (OPSCC) have markedly different patient outcomes. Differences in HPV prevalence between these two patient groups may account for some of this difference, but other molecular markers of prognosis or pathological phenotype have not been established. Copy number gain of oncogenes is a well-established molecular change contributing to HNSCC development. Quantitative PCR was used to explore copy number gains of specific genes (3q-PIK3CA, TP63; 11q13.3-CCND1, ANO1) in tumor DNA recovered from HPSCC (n = 48) and OPSCC (n = 52) patients. Associations between copy number gain, patient demographics, HPV/p16INK4a status and pathological stage were examined. HPV/p16 prevalence in HPSCC and OPSCC groups was 2.1% and 46.0%, respectively. HPSCCs had frequent gains of CCND1 (56.3%) and ANO1 (56.3%) but few gains of PIK3CA (6.3%). By contrast, OPSCCs had significantly fewer CCND1 (23.1%) and ANO1 (17.3%) gains, and significantly more PIK3CA (26.9%) gains. A mutually exclusive relationship between HPV/p16 and 11q13.3 gains was observed in OPSCCs, while PIK3CA and TP63 gains were similar across HPV-associated and smoking/alcohol-associated patients. ANO1 gain was significantly linked to tumor pathology in HPSCC, associating with nodal metastasis and smaller and less invasive tumors at presentation (P = 0.010). Our results provide a convincing link between a specific molecular change and disease phenotype that appears unique to our HPSCC population, supporting a model of 11q13.3 in promoting metastatic disease progression in HNSCC, and suggest a role for ANO1 as a molecular marker of metastatic disease. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Division of Infection and Pathway Medicine, The University of Edinburgh, Little France Crescent, Scotland.
authors.forename: Samuel B
authors.initials: SB
authors.lastname: Pattle
authors.affiliation: Division of Infection and Pathway Medicine, The University of Edinburgh, Little France Crescent, Scotland.
authors.forename: Natasa
authors.initials: N
authors.lastname: Utjesanovic
authors.affiliation: Department of Otolaryngology, The Laurieston Building, NHS Lothian, Edinburgh.
authors.forename: Athena
authors.initials: A
authors.lastname: Togo
authors.affiliation: Western General Hospital, The Edinburgh Cancer Centre, NHS Lothian, Edinburgh.
authors.forename: Lucy
authors.initials: L
authors.lastname: Wells
authors.affiliation: Department of Pathology, Royal Infirmary of Edinburgh, NHS Lothian, Edinburgh.
authors.forename: Brendan
authors.initials: B
authors.lastname: Conn
authors.affiliation: Department of Pathology, Royal Infirmary of Edinburgh, NHS Lothian, Edinburgh.
authors.forename: Hannah
authors.initials: H
authors.lastname: Monaghan
authors.affiliation: Western General Hospital, The Edinburgh Cancer Centre, NHS Lothian, Edinburgh.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Junor
authors.affiliation: Department of Laboratory Medicine, Royal Infirmary of Edinburgh, NHS, Edinburgh.
authors.forename: Ingolfur
authors.initials: I
authors.lastname: Johannessen
authors.affiliation: Scottish HPV Reference Laboratory, Royal Infirmary of Edinburgh, NHS Lothian, Edinburgh.
authors.forename: Kate
authors.initials: K
authors.lastname: Cuschieri
authors.affiliation: Division of Infection and Pathway Medicine, The University of Edinburgh, Little France Crescent, Scotland.
authors.forename: Simon
authors.initials: S
authors.lastname: Talbot
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000556:secondary / Q000821:virology; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D058534:Class I Phosphatidylinositol 3-Kinases; D019938:Cyclin D1 / Q000235:genetics; D056915:DNA Copy Number Variations; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D027383:Papillomaviridae / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000235:genetics* / Q000473:pathology / Q000821:virology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011379:Prognosis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; D019938:Cyclin D1; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human