title: Distinctive clinicopathological associations of amplification of the cortactin gene at 11q13 in head and neck squamous cell carcinomas.
abstract: Amplification of the 11q13 region is a prevalent genetic alteration in head and neck squamous cell carcinoma (HNSCC). We investigated the clinical significance of cortactin (CTTN) and cyclin D1 (CCND1) amplification in both malignant transformation and tumour progression. CTTN and CCND1 amplification was analysed by differential and real-time PCR in a prospective series of laryngeal/pharyngeal carcinomas and archival premalignant tissues. CTTN mRNA and protein expression were respectively determined by real-time RT-PCR and immunohistochemistry, and correlated with gene status. Molecular alterations were associated with clinicopathological parameters and disease outcome. CTTN and CCND1 amplifications were respectively found in 75 (37%) and 90 (45%) tumours. Both correlated with advanced disease; however, only CTTN amplification was associated with recurrence and reduced disease-specific survival (p = 0.0022). Strikingly, CTTN amplification differentially influenced survival depending on tumour site (p = 0.0001 larynx versus p = 0.68 pharynx) and was an independent predictor of reduced survival in the larynx (p = 0.04). CCND1 amplification was detected in early tumourigenesis and increased with the severity of dysplasia. Importantly, CTTN amplification was only found in high-grade dysplasias that progressed to invasive carcinoma. CTTN gene status strongly correlated with mRNA and protein expression. Furthermore, CTTN overexpression correlated significantly with reduced disease-specific survival (p = 0.018). Taken together, these data indicate that CTTN may serve as a valuable biomarker to identify patients with laryngeal tumours at high risk of recurrence and poor outcome.
authors.affiliation: Instituto Universitario de Oncología del Principado de Asturias, Hospital Universitario Central de Asturias, Universidad de Oviedo, Oviedo, Spain. juanpablo.rodrigo@sespa.princast.es
authors.forename: J P
authors.initials: JP
authors.lastname: Rodrigo
authors.forename: D
authors.initials: D
authors.lastname: García-Carracedo
authors.forename: L A
authors.initials: LA
authors.lastname: García
authors.forename: St
authors.initials: S
authors.lastname: Menéndez
authors.forename: E
authors.initials: E
authors.lastname: Allonca
authors.forename: M V
authors.initials: MV
authors.lastname: González
authors.forename: M F
authors.initials: MF
authors.lastname: Fresno
authors.forename: C
authors.initials: C
authors.lastname: Suárez
authors.forename: J M
authors.initials: JM
authors.lastname: García-Pedrero
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002880:Chromosomes, Human, Pair 11; D051356:Cortactin / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D019938:Cyclin D1 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D051356:Cortactin; D012333:RNA, Messenger; D019938:Cyclin D1