title: Cortactin and focal adhesion kinase as predictors of cancer risk in patients with laryngeal premalignancy.
abstract: Novel markers are needed to accurately predict the risk of malignant transformation in laryngeal premalignancies. We therefore investigated the clinical significance of cortactin (CTTN) and focal adhesion kinase (FAK) during laryngeal tumorigenesis and their potential utility as cancer risk markers. CTTN and FAK protein expression and gene amplification were assessed in 82 patients with laryngeal dysplasia and correlated with clinicopathologic parameters and laryngeal cancer risk. Increased CTTN and FAK expression was found respectively in 41 (50%) and 40 (49%) of 82 laryngeal dysplasias; protein expression was maintained or further augmented in the corresponding patient-matched invasive tumors subsequently developed. CTTN and FAK/PTK2 gene amplifications were respectively detected in 10 (12%) and 26 (32%) laryngeal dysplasias. Both CTTN and FAK protein expression increased with the grade of dysplasia; however, CTTN and FAK expression but not histology correlated significantly with increased laryngeal cancer risk (P = 0.009 and P = 0.002, respectively). Patients carrying strong CTTN- or FAK-expressing dysplastic lesions experienced a significantly higher cancer incidence (P = 0.006 and P = 0.001, respectively; log-rank test). Furthermore, FAK expression was an independent predictor of laryngeal cancer development (HR = 3.706, 95% CI: 1.735-7.916; P = 0.001) and the combination of FAK and CTTN showed superior predictive value (HR = 5.042, 95% CI: 2.255-11.274; P < 0.001). Taken together, our findings support the involvement of CTTN and FAK in malignant transformation and provide original evidence for their potential clinical utility as biomarkers for the risk of developing laryngeal cancer.
authors.affiliation: Servicio de Otorrinolaringología, Hospital Universitario Central de Asturias and Instituto Universitario de Oncología del Principado de Asturias, Laboratorio 2 ORL-IUOPA, 33006 Oviedo, Spain.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Rodrigo
authors.forename: Gustavo
authors.initials: G
authors.lastname: Álvarez-Alija
authors.forename: Sofía Tirados
authors.initials: ST
authors.lastname: Menéndez
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Mancebo
authors.forename: Eva
authors.initials: E
authors.lastname: Allonca
authors.forename: Darío
authors.initials: D
authors.lastname: García-Carracedo
authors.forename: Manuel Florentino
authors.initials: MF
authors.lastname: Fresno
authors.forename: Carlos
authors.initials: C
authors.lastname: Suárez
authors.forename: Juana María
authors.initials: JM
authors.lastname: García-Pedrero
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D051356:Cortactin / Q000378:metabolism*; D018572:Disease-Free Survival; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007822:Laryngeal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000473:pathology*; D011230:Precancerous Conditions; D012306:Risk
chemical_list: D014408:Biomarkers, Tumor; D051356:Cortactin; D051416:Focal Adhesion Protein-Tyrosine Kinases