HER2genetic heterogeneity in breast carcinoma

Abstract

AimsTo determine the frequency ofHER2genetic heterogeneity according to the recent American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP) definition (2009) in invasive breast carcinoma, and to identify clinicopathological features that characterise breast carcinomas withHER2genetic heterogeneity.Methods530 invasive breast carcinomas were retrospectively analysed forHER2genetic heterogeneity, and investigated for a potential association ofHER2genetic heterogeneity with otherHER2FISH findings, clinicopathological parameters, oestrogen/progesterone receptor expression and DNA cytometric parameters in breast carcinomas with an equivocal (2+) HER2 immunohistochemical score.ResultsThe overall frequency ofHER2genetic heterogeneity was 14.7% in a cohort of 218 consecutive breast carcinomas.HER2genetic heterogeneity was most frequent in invasive breast carcinomas with an equivocal (2+) HER2 immunohistochemical score. Among the 151 carcinomas lackingHER2amplification, 16.1% showedHER2genetic heterogeneity. In an extended cohort of 345 carcinomas with a (2+) HER2 score, the frequency ofHER2genetic heterogeneity was 41%, and was associated with the absence ofHER2gene clusters, chromosome 17 polysomy, histological tumour grade, DNA ploidy category and 5c exceeding rate.ConclusionHER2genetic heterogeneity according to the ASCO/CAP definition is frequent in breast carcinoma, and is most often present in carcinomas with an equivocal (2+) HER2 score. Many carcinomas withHER2genetic heterogeneity have a negativeHER2amplification status, although they contain a significant number of tumour cells withHER2gene amplification. Single cell scoring of theHER2/17 centromeric probe (CEP17) ratio is necessary to identify carcinomas withHER2genetic heterogeneity, because they lack specific clinicopathological characteristics.