Bethune GC, Mullen JB, Chang MC. Detecting intratumoral heterogeneity in routine breast-HER2 testing: low yield of testing multiple blocks. Ann Diagn Pathol. 2015 Dec;19(6):385-90. doi: 10.1016/j.anndiagpath.2015.08.001. Epub 2015 Aug 15.





Intratumoral heterogeneity can lead to uncertainty in breast carcinoma HER2 testing, both with respect to pathology reporting and clinical significance. The standard practice is to perform breast biomarker testing on a single representative section of tumor; however, concern over heterogeneity often leads to testing on additional tissue blocks. Our objective was to assess the diagnostic yield of testing multiple blocks of a single invasive breast carcinoma.


We performed a retrospective review of 139 consecutive cases (between 2006 and 2012) in which clinical HER2 testing was performed in multiple blocks. Tumor characteristics and HER2 studies (both immunohistochemistry and data from in situ hybridization) were reviewed. Regional differences in morphology and HER2 immunoreactivity were recorded. In situ hybridization was performed in 25 of 139 of the cases; patterns of genetic heterogeneity were reviewed. We audited discordances in HER2 result between blocks.


Testing of multiple blocks yielded no additional HER2 information in 134 (96.4%) of 139 cases. Morphologic differences or heterogeneity in HER2 expression was observed in 22 (15.8%) of 139 of cases. Only 5 of these showed differences in HER2 between blocks, of which 4 were associated with equivocal HER2 immunohistochemistry, and 4 were high-grade.


In the vast majority of cases, even those with heterogeneity, testing of a single block is sufficient for an accurate HER2 determination. High-grade tumors with equivocal HER2 status and observable heterogeneity are more likely to yield a different result on testing of additional blocks.