Impact of HER2 assay sensitivity on the ability to detect tumors with low to ultra-low HER2 expression: A TMA study on more than 10,000 tumors from more than 100 tumor entities

Abstract

Abstract Introduction/Objective Detection of low level HER2 expression is important for therapy with new HER2 inhibitors in breast cancer. HER2 assays with high sensitivity are therefore needed. These may identify low level HER2 expression in various types other than breast cancer. Methods/Case Report A tissue microarray containing >10,000 tissue samples from more than 100 different tumor types and subtypes was analyzed for immunohistochemical expression of HER2 using different immunohistochemistry protocols and anti-HER2 antibodies, including the HercepTest and laboratory developed tests designed for high sensitivity. HER2 IHC evaluation included the recording of HER2 low (1+), ultralow (any staining, less than 1+), and 0 (negative). Results (if a Case Study enter NA) Irrespective of the assay sensitivity all assays showed the expected/tolerable association with HER2 FISH data in 308 breast cancers. In non-breast cancers, the use of different assays yielded variable rates of low or ultra-low HER2 expression in different tumor entities. For example, low (1+) and ultra-low (+) expression was observed in 7-24% (1+) and 11-28% (+) of serous ovarian cancers, 6.2-24% (1+) and 3.4-19% (+) of endometrioid endometrial cancers, 5.5-14% (1+) and 7.7-13% (+) of intestinal gastric cancers, 1.8-9.2% (1+) and 4.5- 11% (+) of ductal adenocarcinomas of the pancreas, 19-33% (1+) and 5.5-11% (+) of muscle invasive urinary bladder cancers, 2.9-16% (1+) and 4.3-12% (+) of adenocarcinomas of the colon. Conclusion Low level HER2 expression occurs commonly in many cancer types. The rate of identifiable tumors with HER2 low or HER2 ultra-low expression varies depending on assay parameters that can easily be modified. Irrespective of assay sensitivity, our data identify various tumor entities with significant fractions of “HER2-low” cases that might benefit from therapy with new antibody drug conjugates.