Fluorescent In Situ Hybridization for Human Epidermal Growth Factor Receptor 2 Assessment in Breast Cancer: Is It Applicable As a Primary Test?

Abstract

TO THE EDITOR: Recently, Sauter et al reviewing the American Society of Clinical Oncology–College of American Physicians Guidelines for determining human epidermal growth factor receptor 2 (HER2) status in breast cancer patients, suggest fluorescent in situ hybridization (FISH) as the primary HER2 assay method to select women with breast cancer candidate to targeted therapy. Undoubtedly, the paper has the merit of performing an extremely accurate analysis of all the issues relating to the immunohistochemical preanalytic and analytic critical steps which are responsible for the difficulties and the interlaboratory differences in test interpretation. However, the following points should be addressed: It is true that FISH success rate is high, compared with immunohistochemistry (IHC); however, in daily laboratory practice, FISH analysis on formalin-fixed paraffin-embedded tissues present a range of technical problems at least paralleling those met in IHC, as already stated by Peterson et al in 2004. We agree with Sauter et al’s opinion on the interlaboratory reproducibility of FISH test, nevertheless, we believe that only the combination of FISH evaluation with IHC can reduce the possibility of diagnostic pitfalls (see Dowsett et al). Sauter et al do not mention the difference in the performing time of FISH in comparison with IHC and the necessity of dedicated experienced technicians to make the analysis. We totally agree with the large spectrum analysis of the costs made by Sauter et al, but restricting the same analysis to the “pathology laboratory economy,” we are not so sure that the choice to make only FISH for HER2 determination is really sustainable. In conclusion, although we completely share the Sauter et al’s opinion about the crucial role of FISH in correct molecular characterization of breast cancers, and the article has the unquestionable merit of examining all the emergent problems about this topic, we in part disagree on the conclusions both for the points mentioned here and because we think that what Sauter et al propose is not concretely applicable on a large scale. In using FISH as the primary test for HER2 status determination, there would be an increment of the technical and medical daily workload and increased pathology laboratory costs that could not be borne by all the peripheral laboratories. Finally, we believe that both the oncologists and pathologists should not lose trust in IHC, at least as a primary assessment method of HER2 expression.