Epidermal growth factor receptor expression and gene copy number in the risk of oral cancer.
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.
Taoudi Benchekroun
Mohammed
M
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, USA.
Saintigny
Pierre
P
Thomas
Sufi M
SM
El-Naggar
Adel K
AK
Papadimitrakopoulou
Vassiliki
V
Ren
Hening
H
Lang
Wenhua
W
Fan
You-Hong
YH
Huang
Jianhua
J
Feng
Lei
L
Lee
J Jack
JJ
Kim
Edward S
ES
Hong
Waun Ki
WK
Johnson
Faye M
FM
Grandis
Jennifer R
JR
Mao
Li
L
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology* / Q000235:genetics / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007972:Leukoplakia, Oral / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000453:epidemiology* / Q000235:genetics / Q000378:metabolism; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012307:Risk Factors
D014408:Biomarkers, Tumor; D066246:ErbB Receptors