title: EGFR gene copy number alteration is a better prognostic indicator than protein overexpression in oral tongue squamous cell carcinomas.
abstract: Although epidermal growth factor receptor (EGFR) is particularly important in the pathogenesis of head and neck squamous cell carcinomas (HNSCCs), conflicting data have been reported on the correlation between EGFR copy number and survival and the association between EGFR copy number and protein expression. Anatomical site of the tumour in HNSCCs may likely contribute to the discordance of the above points as EGFR expression may differ between the sub-sites of HNSCCs. Thus, in this study, we focused on oral tongue squamous cell carcinomas (OTSCCs). To investigate the association between EGFR copy number alteration and overexpression and to determine which is the more reliable prognostic indicator, Fluorescence in situ hybridisation (FISH) and immunohistochemical staining (IHC) were performed at a single institution on samples from 89 patients with OTSCCs undergoing surgery as the primary treatment modality. Thirty-two (36%) of 89 cases demonstrated an EGFR copy number alteration. EGFR protein expression was found in all 89 cases, of which 82.0% showed overexpression. No significant correlation was found between gene copy number and protein overexpression. Gene copy number alteration was significantly associated with reduced disease-free survival (P=0.048) and overall survival (P=0.001). Multivariate Cox proportional hazards analysis demonstrated that EGFR copy number increase was significantly correlated with overall survival (P=0.001). EGFR copy number status is a more reliable indicator than protein overexpression of the survival rate in OTSCCs. FISH analysis of the EGFR status is useful in predicting poor prognosis in OTSCCs.
authors.affiliation: Maxillofacial Surgery, Maxillofacial Reconstruction and Function, Division of Maxillofacial and Neck Reconstruction, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan. y-nakata.mfs@tmd.ac.jp
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Nakata
authors.forename: Narikazu
authors.initials: N
authors.lastname: Uzawa
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Takahashi
authors.forename: Jun
authors.initials: J
authors.lastname: Sumino
authors.forename: Chieko
authors.initials: C
authors.lastname: Michikawa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sato
authors.forename: Itaru
authors.initials: I
authors.lastname: Sonoda
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Ohyama
authors.forename: Norihiko
authors.initials: N
authors.lastname: Okada
authors.forename: Teruo
authors.initials: T
authors.lastname: Amagasa
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000032:analysis / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007564:Japan; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors; D014062:Tongue Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C512478:EGFR protein, human; D066246:ErbB Receptors