Intratumoral Heterogeneity of HER-2/neu Gene Amplification in Breast Cancer
H Seol, HE Lee, SW Kim, JH Kim, G Choe, SY Park. Seoul National University Bundang Hospital, Seongnam, Korea
Background: Genetic heterogeneity of HER-2 gene amplification has been reported in variable frequencies in breast cancers.
Design: To determine the frequency of intratumoral heterogeneity of HER-2 gene amplification and find the characteristics of tumor with it, we evaluated 3 cores of tissue microarray from different areas of each tumor by dual color fluorescence in situ hybridization in 50 invasive breast carcinomas (IBCs) with HER-2 gene amplification on whole tissue sections and 2+ or 3+ HER-2 protein overexpresssion. HER-2 gene amplification was scored by the American Society of Clinical Oncology/College of American Pathologist (ASCO/CAP) criteria. HER-2 genetic heterogeneity was defined as the existence of tumor cells with a ratio higher than 2.2 in 5% to 50% of tumor cells according to CAP guideline.
Results: Of the 50 IBCs, 24 cases (48%) showed high grade (HER-2/CEP17 ratio = or > 4), 15 (30%) showed low grade (ratio >2.2 to <4.0) and four cases (8%) showed high or low grade amplification in three cores. Seven cases (14%) showed discordant results for HER-2 amplification. Of two cases with high grade amplification in a core, one case showed not amplified pattern in other cores, and the other case showed not amplified pattern or equivocal HER-2 gene amplification in other cores. Of five cases with low grade amplification in at least one core, two case revealed equivocal HER-2 gene amplification and the other two cases revealed chromosome 17 polysomy in other cores. HER-2 genetic heterogeneity was found in six (12%) cases, all of which showed discordant results for HER-2 gene amplification.
Conclusions: Assessment of HER-2 gene amplification seems to be not significantly affected by intratumoral heterogeneity in most IBCs. However, HER-2 genetic heterogeneity is present in a subset of IBCs, especially in some cases with low grade amplification and rare cases with high grade amplification. Further studies will be needed to determine the clinical significance of HER-2 genetic heterogeneity in breast cancers.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 34, Monday Morning