Copy number alterations of the epidermal growth factor receptor (EGFR)
gene have been extensively analyzed in different cancers, but no data
ate available for primary malignant melanoma. The aim of the present
study was to simultaneously investigate the EGFR gene and chromosome 7
copy number alterations in 81 cutaneous malignant melanomas by
interphase FISH and correlate the data with clinicopathological
parameters of patients. EGFR mRNA levels were detected by Affymetrix
GeneChip Human Genome U133 Plus 2.0 expression arrays for 16 lesions.
Both increased gene dosage and chromosome 7 alterations were found in
70% of tumors. Extra EGFR copies were detected in an additional 10% of
samples. Polysomy 7 was associated with EGFR gene amplification.
Significant correlation was found between EGFR alterations and
histological subtypes, tumor thickness, ulceration and metastases
formation. Amplification was significantly higher in lesions that
developed metastases within 2 years after surgical excision of the
primary tumor. Gene copy alterations were associated with elevated mRNA
expression in 77% of lesions when compared to tumors with disomic EGFR
status, the correlation was not directly proportional to gene copy
number. Associations between protein expression and mRNA levels were
even less prominent. In conclusion, our study indicates that
amplification of the EGFR gene and polysomy 7 are frequent alterations
in primary melanomas and are associated with bad prognosis. Further
studies are required to clarify whether melanoma patients with EGFR
alterations can benefit from anti-EGFR therapy. (C) 2007 Wiley-Liss,
Inc.
