PMID- 20570883 OWN - NLM STAT- MEDLINE DCOM- 20100830 LR - 20220410 IS - 1940-6215 (Electronic) IS - 1940-6207 (Print) IS - 1940-6215 (Linking) VI - 3 IP - 7 DP - 2010 Jul TI - Epidermal growth factor receptor expression and gene copy number in the risk of oral cancer. PG - 800-9 LID - 10.1158/1940-6207.CAPR-09-0163 [doi] AB - 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. CI - 2010 AACR. FAU - Taoudi Benchekroun, Mohammed AU - Taoudi Benchekroun M AD - Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, USA. FAU - Saintigny, Pierre AU - Saintigny P FAU - Thomas, Sufi M AU - Thomas SM FAU - El-Naggar, Adel K AU - El-Naggar AK FAU - Papadimitrakopoulou, Vassiliki AU - Papadimitrakopoulou V FAU - Ren, Hening AU - Ren H FAU - Lang, Wenhua AU - Lang W FAU - Fan, You-Hong AU - Fan YH FAU - Huang, Jianhua AU - Huang J FAU - Feng, Lei AU - Feng L FAU - Lee, J Jack AU - Lee JJ FAU - Kim, Edward S AU - Kim ES FAU - Hong, Waun Ki AU - Hong WK FAU - Johnson, Faye M AU - Johnson FM FAU - Grandis, Jennifer R AU - Grandis JR FAU - Mao, Li AU - Mao L LA - eng GR - P30 CA016672/CA/NCI NIH HHS/United States GR - P50 CA097007/CA/NCI NIH HHS/United States GR - R01 CA077308/CA/NCI NIH HHS/United States GR - P50 CA97007/CA/NCI NIH HHS/United States GR - P30 CA16672/CA/NCI NIH HHS/United States GR - P01 CA106451/CA/NCI NIH HHS/United States GR - P01 CA106451-030003/CA/NCI NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20100622 PL - United States TA - Cancer Prev Res (Phila) JT - Cancer prevention research (Philadelphia, Pa.) JID - 101479409 RN - 0 (Biomarkers, Tumor) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM CIN - Cancer Prev Res (Phila). 2010 Jul;3(7):797-9. PMID: 20570884 MH - Biomarkers, Tumor/genetics/metabolism MH - Carcinoma, Squamous Cell/*epidemiology/genetics/metabolism MH - ErbB Receptors/*genetics/*metabolism MH - Female MH - *Gene Dosage MH - Humans MH - Leukoplakia, Oral/genetics/metabolism/pathology MH - Male MH - Middle Aged MH - Mouth Neoplasms/*epidemiology/genetics/metabolism MH - Precancerous Conditions/genetics/metabolism/*pathology MH - Risk Factors PMC - PMC2900459 MID - NIHMS167990 EDAT- 2010/06/24 06:00 MHDA- 2010/08/31 06:00 PMCR- 2011/07/01 CRDT- 2010/06/24 06:00 PHST- 2010/06/24 06:00 [entrez] PHST- 2010/06/24 06:00 [pubmed] PHST- 2010/08/31 06:00 [medline] PHST- 2011/07/01 00:00 [pmc-release] AID - 1940-6207.CAPR-09-0163 [pii] AID - 10.1158/1940-6207.CAPR-09-0163 [doi] PST - ppublish SO - Cancer Prev Res (Phila). 2010 Jul;3(7):800-9. doi: 10.1158/1940-6207.CAPR-09-0163. Epub 2010 Jun 22.