Abstract

Cancer heterogeneity is a great challenging factor within the innovative emerging approach in the field of Cancer Precession Medicine. Thus oncologists and pathologists are facing an extraordinary challenge in managing those patients. Cancer heterogeneity is well known in various cancers such as breast and gastric cancers precisely the heterogeneity on human epidermal growth receptor 2 (HER2), our focused gene-mutation case in this study. Unfortunately, HER2 heterogeneity is not well understood yet, but its impact on a considerable number of patients is well documented. Therefore, this study is aiming to investigate the Her2 gene heterogeneity in gastroesophageal cancer patients.  Sequential serial tissue sections were examined at different levels/depths for HER2 protein expressions by applying the standard immunohistochemistry (IHC) technique. The sequential serial sections were also used for testing the HER2 gene amplification hyperdization technique (ISH). HER2 status was classified as positive or negative and HER2 heterogeneous or homogenous for each individual histology representative and site examined according to the standard HER2 testing system in use for gastric cancers. There was an obvious variation in Her2 protein expression which was expected, while all blocks have shown also variable Her2 protein intensity scoring, none was amplified as all sections examined scored below (1.8) ratio (HER2 gene: centromere). Our study shows the current routine of HER2 testing of a single test stands a great chance of miss-diagnosis for positive HER2 mutation in GOJ patients. Multiple sections to be tested for negative cases could save lives and therefore, are highly recommended.

Keywords: HER2, Heterogeneity, Gastroesophageal junction cancer, Trustazumab, Immunohistochemistry, and Precision medicine