Protein overexpression and gene amplification of epidermal growth factor receptor in nonsmall cell lung carcinomas. An immunohistochemical and fluorescence in situ hybridization study.
BACKGROUND
Recently, molecular therapies targeting epidermal growth factor receptor (EGFR) have been developed for clinical use. The current study was conducted to determine 1) the exact frequency of EGFR protein overexpression, 2) the correlation between protein overexpression and EGFR amplification, and 3) the correlation between the status of the genetic and clinicopathologic features in nonsmall cell lung carcinomas (NSCLC).


METHODS
In total, 181 NSCLC samples were examined immunohistochemically using an antibody against EGFR, and tumor cells that exhibited overexpression were examined further for EGFR amplification by fluorescence in situ hybridization.


RESULTS
Overexpression of EGFR protein was found in 34% of the tumors. Among these, EGFR amplification was demonstrated in 74%. High-level gene amplification was found exclusively in tumors cells with high protein expression. In most of these tumors, cells that exhibited EGFR overexpression and gene amplification were distributed heterogeneously, even within a single tumor nodule. Statistically, EGFR overexpression was correlated significantly with lymph node metastasis and with a more advanced pathologic stage. Moreover, in adenocarcinomas, gene amplification was correlated significantly with lymph node metastasis and tended to be correlated with a more advanced pathologic stage.


CONCLUSIONS
The overexpression of EGFR in NSCLC was accompanied predominantly, but not exclusively, by gene amplification. It is important to evaluate not only protein overexpression but also the EGFR status to design adjuvant therapies for patients with NSCLC, because specimens that exhibit both protein overexpression and gene amplification may predict eventual lymph node metastasis and, possibly, aggressive tumor behavior.
Suzuki
Shioto
S
Department of Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan.
Dobashi
Yoh
Y
Sakurai
Hiroyuki
H
Nishikawa
Keiichi
K
Hanawa
Mitsuhiko
M
Ooi
Akishi
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000401:mortality* / Q000473:pathology*; D015331:Cohort Studies; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics / Q000401:mortality* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D018570:Risk Assessment; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D066246:ErbB Receptors