Neoplasma Vol.52, p.338-343, 2005
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Title: Epidermal growth factor receptor - its expression and copy numbers
of EGFR gene in patients with head and neck squamous cell
carcinomas
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Author: M., MRHALOVA
; J., PLZAK
; J., BETKA
; R., KODET
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Abstract: Signaling pathways activated by epidermal growth factor receptor
(EGFR) are pathogenetically involved in the development
of head and neck squamous cell carcinomas (HNSCC). A monoclonal
antibody against the EGFR protein blocking the
receptor activity (cetuximab – Erbitux – C225) is now available
for therapeutic applications. The mechanisms of EGFR protein
overexpression are poorly understood. Regulatory pathways, EGFR
gene structural changes or its amplification may be
involved. The aim of the study was to evaluate expression of the
EGFR protein in patients with HNSCC, to identify EGFR
gene copy numbers, and to find out whether the protein
overexpression is associated with the EGFR gene amplification. In
the case of a pathogenetical link of the EGFR gene amplification
and the protein overexpression it would be useful to employ
both diagnostic approaches to identify patients eligible for
cetuximab therapy. We investigated 33 patients with
HNSCC. The expression of EGFR protein was evaluated by
immunohistochemistry, copy numbers of EGFR gene and the
numbers of chromosome 7 centromeric signals were investigated by
fluorescence in situ hybridization on interphasic nuclei
(I-FISH). Histological sections from formalin fixed and paraffin
embedded tissues were used. We observed three types of
EGFR protein expression (homogeneous 3+ membrane positivity in 13
patients; membrane positivity varying from 1+ to 3+
in 12 patients; a strong membrane positivity at the periphery of
the tumor cell clusters in 5 patients). In two cases the results
were difficult to interpret. In one case single tumor cells only
were positive. Numerical changes of chromosome 7 were present
in 23 patients. We found the EGFR gene amplification in seven
patients. The tumor cells with amplification of the EGFR
gene were generally infrequent and were localized in small
clusters, or they were randomly dispersed between the tumor cell
population without the gene amplification. We did not find any
correlation between the EGFR gene amplification and the
EGFR protein overexpression. Thus, amplification of the EGFR gene
is not pathogenetically involved in the EGFR protein
overexpression. From the diagnostic aspect a standardized
immunohistochemical assessment of the EGFR protein expression
appears sufficient for detection of the EGFR status. Criteria for
cetuximab treatment in patients with HNSCC may differ
from those already used for patients with colorectal carcinomas
and should take different patterns of the EGFR protein
overexpression into consideration.
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Keywords: head and neck squamous cell carcinoma, epidermal growth factor
receptor, protein expression, gene copy numbers, cetuximab
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Year: 2005, Volume: 52, Issue: |
Page From: 338, Page To: 343 |
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