EGFR gene copy number heterogeneity in fine-needle aspiration cytology from breast carcinomas determined by chromogenic in situ hybridization.

Most studies have shown epidermal growth factor receptor(EGFR) overexpression to be associated with poor prognosticfactors in breast carcinomas. The relationship to EGFR genecopy number is unclear. The aim of our study was to investigatethe heterogeneity of the EGFR gene copy number in breast car-cinomas. The material consisted of air-dried smears from 29breast carcinomas and 3 breast cancer cell lines (MCF-7,SKBR3, and T47D). Chromogenic in situ hybridization (CISH)was done using chromogenic detection. The mean signal num-bers for EGFR gene and chromosome 7 as well as the EGFRgene/chromosome 7 centromere probe (CEP7) ratio wererecorded. Immunohistochemical (IHC) staining was done on thecorresponding paraffin sections.The copy number of the EGFR gene in each tumor/cell lineranged from 1.2 to 5.6. The EGFR gene/CEP7 ratio showed abiological continuum ranging from 0.59 to 1.94 with a mean of1.04. EGFR gene copy loss was found in 16.6% of caseswhereas copy gain was demonstrated in 19.4%. There was norelationship between IHC protein expression of EGFR andEGFR gene copy number or EGFR gene/CEP7 ratio.In conclusion, most breast carcinomas had a balanced EGFRgene/CEP7 copy number with a mean ratio of 1.04. Almostequal subpopulations revealed limited copy gain and copy loss.EGFR high dosage amplification, like in HER-2, was not demon-strated. Demonstration of EGFR gene copy loss might have apotential as a surrogate marker for EGFR gene mutation and/ordeletion. Diagn. Cytopathol. 2005;33:228–232.