Determination of HER2 Amplification by In Situ Hybridization: When Should Chromosome 17 also be Determined?

Our purpose was to determine the accuracy of diagnosis of HER2 amplification by analysis of HER2 copy number. HER2 and chromosome 17 were measured by dual-color fluorescence in situ hybridization in breast cancer samples. At a HER2 copy number of 2 to less than 3, 16 (3.3%) of 488 cases had HER2 amplification; and at a copy number of 3 to less than 4, 32 (16.4%) of 195 cases were amplified. The proportion of cases with HER2 amplification increased considerably at HER2 copy numbers of 4 to less than 7: 50.0% at 4 to less than 5: 67.5 % at 5 to less than 6, and 77.3% at 6 to less than 7. Virtually all cases were amplified at HER2 copy numbers of 7 or more. We recommend that all breast cancer cases with a HER2 copy number of 2 to 7 determined by single-color in situ hybridization should also be analyzed for chromosome 17 to obtain a more accurate diagnosis of HER2 amplification.