OBJECTIVETo introduce the College of American Pathologists/American College of Medical Genetics Cytogenetics Resource Committee criteria for genetic heterogeneity (GH) in HER2 testing, and investigate the clinicopathological significance of HER2 genetic heterogeneity in invasive breast cancer.

METHODSThe clinical parameters of 100 cases of invasive breast carcinomas were collected. HER2 expression level and HER2 gene copy number in formalin-fixed and paraffin embedded tumor samples were detected by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), and the relationship between HER2 gene GH and clinicopathological characteristics were analyzed.

RESULTSAmong the 100 patients, HER2 gene GH was observed in 20 (20%) cases. When the number of HER2 amplified cells was more than 25%, the frequencies of FISH positive were higher than those cases with less than 25% HER2 amplified cells. The results showed that HER2 gene GH was associated with the degree of HER2 protein expression (P=0.004), and ER expression (P=0.002).

CONCLUSIONHER2 gene GH may be correlated with the HER2 protein IHC 1+/2+, and ER expression in breast carcinoma. It is important for doctors to avoid ignoring or only counting FISH positive cells leading to incorrect diagnosis for these patients.