EGFR gene copy number alterations in primary cutaneous malignant melanomas are associated with poor prognosis.
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.
Rákosy
Zsuzsa
Z
Department of Preventive Medicine, Faculty of Public Health, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
Vízkeleti
Laura
L
Ecsedi
Szilvia
S
Vokó
Zoltán
Z
Bégány
Agnes
A
Barok
Márk
M
Krekk
Zsuzsa
Z
Gallai
Mónika
M
Szentirmay
Zoltán
Z
Adány
Róza
R
Balázs
Margit
M
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
D012333:RNA, Messenger; D066246:ErbB Receptors