Epidermal Growth Factor Receptor Expression and Gene Copy Number in the Risk of Oral Cancer
- 1 July 2010
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Cancer Prevention Research
- Vol. 3 (7), 800-809
- https://doi.org/10.1158/1940-6207.capr-09-0163
Abstract
Leukoplakia is the most common premalignant lesion of the oral cavity. Epidermal growth factor receptor (EGFR) abnormalities are associated with oral tumorigenesis and progression. We hypothesized that EGFR expression and gene copy number changes are predictors of the risk of an oral premalignant lesion (OPL) progressing to oral squamous cell carcinoma (OSCC). A formalin-fixed, paraffin-embedded OPL biopsy specimen was collected from each of 162 patients in a randomized controlled clinical trial. We assessed EGFR expression by immunohistochemistry with two methods: a semiquantitative analysis (145 evaluable specimens) and an automated quantitative analysis (127 evaluable specimens). EGFR gene copy number was assessed by fluorescence in situ hybridization (FISH) in a subset of 49 OPLs with high EGFR expression defined by the semiquantitative analysis. We analyzed EGFR abnormalities for associations with OSCC development. High EGFR expression occurred in 103 (71%) of the 145 OPLs and was associated with a nonsignificantly higher risk of OSCC (P = 0.10). Twenty (41%) of 49 OPLs assessed by FISH had an increased EGFR gene copy number (FISH-positive). Patients with FISH-positive lesions had a significantly higher incidence of OSCC than did patients with FISH-negative (a normal copy number) lesions (P = 0.0007). Of note, 10 of 11 OSCCs that developed at the site of the examined OPL were in the FISH-positive group, leaving only one FISH-negative OPL that did so (P < 0.0001). Our data indicate that an increased EGFR gene copy number is common in and associated with OSCC development in patients with OPLs expressing high EGFR, particularly OSCC developing at the site of a high-expression OPL; they also suggest that EGFR inhibitors may prevent oral cancer in patients with OPLs having an increased EGFR gene copy number. Cancer Prev Res; 3(7); 800–9. ©2010 AACR.Keywords
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This publication has 53 references indexed in Scilit:
- ΔNp63 Overexpression, Alone and in Combination with Other Biomarkers, Predicts the Development of Oral Cancer in Patients with LeukoplakiaClinical Cancer Research, 2009
- Intratumoral Epidermal Growth Factor Receptor Antisense DNA Therapy in Head and Neck Cancer: First Human Application and Potential Antitumor MechanismsJournal of Clinical Oncology, 2009
- Randomized Trial of 13-cis Retinoic Acid Compared With Retinyl Palmitate With or Without Beta-Carotene in Oral PremalignancyJournal of Clinical Oncology, 2009
- Platinum-Based Chemotherapy plus Cetuximab in Head and Neck CancerNew England Journal of Medicine, 2008
- EGFR, p16, HPV Titer, Bcl-xL and p53, Sex, and Smoking As Indicators of Response to Therapy and Survival in Oropharyngeal CancerJournal of Clinical Oncology, 2008
- Combined Targeting of Epidermal Growth Factor Receptor, Signal Transducer and Activator of Transcription-3, and Bcl-XLEnhances Antitumor Effects in Squamous Cell Carcinoma of the Head and NeckPublished by American Society for Pharmacology & Experimental Therapeutics (ASPET) ,2008
- Fundamental Differences in Cell Cycle Deregulation in Human Papillomavirus–Positive and Human Papillomavirus–Negative Head/Neck and Cervical CancersCancer Research, 2007
- Identification of biomarkers that distinguish human papillomavirus (HPV)-positive versus HPV-negative head and neck cancers in a mouse modelProceedings of the National Academy of Sciences, 2006
- Human Papillomavirus Types in Head and Neck Squamous Cell Carcinomas Worldwide: A Systematic ReviewCancer Epidemiology, Biomarkers & Prevention, 2005
- Low-Dose Isotretinoin Versus -Carotene to Prevent Oral Carcinogenesis: Long-term Follow-upJNCI Journal of the National Cancer Institute, 1997