Simultaneous Assessment of Cyclin D1 and Epidermal Growth Factor Receptor Gene Copy Number for Prognostic Factor in Oral Squamous Cell Carcinomas / Oral Science International

ABSTRACT

Cyclin D1 gene (<i>CCND1</i>) numerical aberrations are independent prognostic indicators of head and neck squamous cell carcinomas (HNSCCs). High epidermal growth factor receptor gene (<i>EGFR</i>) copy number is associated with poor prognosis in lung cancer, but such findings are controversial in oral SCCs (OSCCs). We analyzed copy number status in <i>CCND1</i> and <i>EGFR</i> in OSCC patients and its association with clinical outcome.<i>EGFR</i> and <i>CCND1</i> statuses were analyzed in 85 OSCC patients by fluorescence <i>in situ</i> hybridization (FISH) of specimens obtained by fine-needle aspiration biopsy.<i>CCND1</i> numerical aberration was found in 35 of 85 tumors (41%), and aberrant <i>EGFR</i> copy number was observed in 36 (42%). Gene amplification (GA) was dominant among <i>CCND1</i> copy number changes (14/3540%). Balanced trisomy (BT) was the most frequently observed <i>EGFR</i> aberration (17/3647%). In a multivariate Cox's proportional hazards analysis, <i>CCND1</i> GA was correlated with disease-free survival (<i>P</i><0.001), whereas <i>EGFR</i> BT was significantly correlated with overall survival (<i>P</i>=0.001). Patients with a combination of <i>CCND1</i> GA and/or <i>EGFR</i> BT had significantly poorer clinical outcome.<i>CCND1</i> and <i>EGFR</i> copy number changes were frequent in OSCC and had differing aberration patterns. <i>CCND1</i> GA and <i>EGFR</i> BT statuses by dual-color FISH were the predominant predictors of clinical outcome. Further investigation is needed to determine the implications for EGFR inhibitor therapy in OSCC.