title: EGFR gene copy number alterations in primary cutaneous malignant melanomas are associated with poor prognosis.
abstract: Copy number alterations of the epidermal growth factor receptor (EGFR) gene have been extensively analyzed in different cancers, but no data are 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.
authors.affiliation: Department of Preventive Medicine, Faculty of Public Health, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Rákosy
authors.forename: Laura
authors.initials: L
authors.lastname: Vízkeleti
authors.forename: Szilvia
authors.initials: S
authors.lastname: Ecsedi
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Vokó
authors.forename: Agnes
authors.initials: A
authors.lastname: Bégány
authors.forename: Márk
authors.initials: M
authors.lastname: Barok
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Krekk
authors.forename: Mónika
authors.initials: M
authors.lastname: Gallai
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Szentirmay
authors.forename: Róza
authors.initials: R
authors.lastname: Adány
authors.forename: Margit
authors.initials: M
authors.lastname: Balázs
mesh_terms: D000328:Adult; D000368:Aged; D015153:Blotting, Western; D002897:Chromosomes, Human, Pair 7; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase; D008297:Male; D008545:Melanoma / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D018613:Microscopy, Confocal; D008875:Middle Aged; D011123:Polyploidy; D011237:Predictive Value of Tests; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000150:complications / Q000235:genetics* / Q000473:pathology; D012883:Skin Ulcer / Q000209:etiology
chemical_list: D012333:RNA, Messenger; D066246:ErbB Receptors