Epidermal growth factor receptor protein expression and gene amplification in normal, hyperplastic, and cancerous glottic tissue: immunohistochemical and fluorescent in situ hybridization study on tissue microarrays.
OBJECTIVE
To evaluate the importance of epidermal growth factor receptor (EGFR) protein overexpression and gene amplification in carcinogenesis of glottic cancer.


METHODS
In order to evaluate EGFR expression at protein and gene level, immunohistochemical (IHC) analysis and fluorescent in situ hybridization (FISH) were performed on tissue microarrays of laryngeal tissue (145 samples) -- 38 samples of normal mucosa, 46 samples of hyperplastic lesions, and 61 samples of cancerous lesions.


RESULTS
Membranous (mEGFR) and cytoplasmic (cEGFR) EGFR expression was significantly different between the analyzed groups. The differences were most striking in the suprabasal-transforming zone. IHC evaluation showed that high and low mEGFR staining contributed to the differentiation of dysplastic lesions, simple hyperplasia, and cancerous tissue, as well as between different degrees of atypia in hyperplastic lesions (P<0.050). EGFR gene amplification was not found in simple and abnormal hyperplastic lesions, but it was confirmed in 2/21 atypical hyperplasias, indicating that gene amplification can facilitate identification of malignant potential in hyperplastic lesions. In cancerous tissue, EGFR gene amplification was found in 8/50 samples. EGFR gene amplification was found in preinvasive cancer in one patient. In invasive carcinomas, gene amplification was not associated with stage or grade. Carcinomas with gene amplification showed significantly higher cEGFR expression (basal layer P=0.003; suprabasal layer P=0.002).


CONCLUSIONS
This study confirmed an increase in EGFR protein expression and gene amplification with the increase in biological aggressiveness of glottic lesions. A correlation between EGFR gene amplification and protein expression was established. Gene amplification proved to be an early event in glottic carcinogenesis, indicating its importance for glottic cancer prevention, early detection, and protocol selection.
Braut
Tamara
T
Department of Otorhinolaryngology, Head and Neck Surgery, Clinical Hospital Center Rijeka, Kresimirova 42, 51000, Rijeka, Croatia.
Krstulja
Mira
M
Kujundzić
Milodar
M
Manestar
Dubravko
D
Hadzisejdić
Ita
I
Jonjić
Nives
N
Grahovac
Blazenka
B
Manestar
Darko
D
D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005784:Gene Amplification; D005931:Glottis / Q000378:metabolism*; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000473:pathology*
D066246:ErbB Receptors