Original scientific paper
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
Tamara Braut
; Department of Otorhinolaryngology Head and Neck Surgery, Clinical Hospital Center Rijeka, Croatia
Mira Krstulja
; Department of Pathology, School of Medicine, University of Rijeka, Croatia
Milodar Kujundžić
; Department of Otorhinolaryngology Head and Neck Surgery, Clinical Hospital Center Rijeka, Croatia
Dubravko Manestar
; Department of Otorhinolaryngology Head and Neck Surgery, Clinical Hospital Center Rijeka, Croatia
Ita Hadžisejdić
; Department of Pathology, School of Medicine, University of Rijeka, Croatia
Nives Jonjić
; Department of Pathology, School of Medicine, University of Rijeka, Croatia
Blaženka Grahovac
; Department of Pathology, School of Medicine, University of Rijeka, Croatia
Darko Manestar
; Department of Otorhinolaryngology Head and Neck Surgery, Clinical Hospital Center Rijeka, Croatia
Abstract
Aim To evaluate the importance of epidermal growth factor receptor
(EGFR) protein overexpression and gene amplification in
carcinogenesis of glottic cancer.
Method 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.
Keywords
EGFR; quantitative immunohistochemistry; FISH; glottic cancer; tissue microarray; EGFR-targeted therapies
Hrčak ID:
47857
URI
Publication date:
15.8.2009.
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