Reproducibility in the Assessment of HER2 DISH in Breast Cancer

Abstract

OBJECTIVE: HER2 gene status is an important biological marker that determines both the prognosis and response to Trastuzumab in patients with breast cancers. Although FISH assay has long been used to determine the HER2 gene copy number, DISH is gaining popularity since it can be assessed with a conventional microscope. The DISH test relies on an individual inspection however, so inter-observer variation may be an issue. MATERIALS AND METHODS: In the current study, reproducibility in the assessment of HER2 DISH test was evaluated in 69 breast cancer samples with HER2 IHC score 2+ and 3+. Two independent investigators evaluated the digitallycaptured images of DISH, without the knowledge of HER2 IHC status. RESULTS: The HER2/CEP17 ratio obtained from both observers were highly correlated (Rho = 0.883, p < 0.001). Based on the ASCO 2013 guideline, agreement of both investigators for HER2 gene diagnosis was 92.75 % (ĸ = 0.848). The HER2/CEP17 ratio of the discordant cases ranged from 1.6 (non-amplifi ed HER2) to 2.6 (low level of HER2 gene amplifi cation). CONCLUSION: It is concluded that the DISH method produces good reproducibility between independent observers, and the result also implies that the HER2 gene copy number is fairly homogenous across an individual breast cancer sample.