Her2 testing in gastric cancer

• Published in: Der Pathologe 2010-05, Vol.31 (3), p.208-217
• Main Authors: Rüschoff, J, Nagelmeier, I, Baretton, G, Dietel, M, Höfler, H, Schildhaus, H.U, Büttner, R, Schlake, W, Stoss, O, Kreipe, H.H
• Format: Article
• Language: eng ; ger
• Subjects: Fluoreszenz-in-situ-Hybridisierung; Her2-Diagnostik; Immunhistochemie; Magenkarzinom
• ISSN: 0172-8113; 1432-1963
• DOI: 10.1007/s00292-010-1278-1

Based on data from a large multicenter phase III trial (ToGA study) trastuzumab has very recently been approved by the EMEA for metastatic gastric cancer and adenocarcinoma of the gastro-esophageal junction. Only patients with tumors which over express Her2 as defined by IHC2+ and a confirmatory FISH+ result, or IHC 3+, determined by an accurate and validated assay are eligible for trastuzumab therapy. However, testing of Her2 status by immunohistochemistry (IHC) differs from breast cancer in core aspects: 1. IHC2+/3+ is scored even though membranous staining is incomplete if membrane staining is clearly detectable even at low magnification (2.5x/5x, 3+) or medium magnification (10x/20x, 2+). 2. Additionally, membrane staining at the appropriate intensity found in at least 10% of tumor cells is restricted to resection specimens. Evaluation of Her2 in situ hybridization (ISH) is similar to breast cancer with ratio values of ≥2.0 indicating Her2 gene amplification. Taking these modifications into account and defining the HER2 positive subgroup as IHC 3+ and IHC2+/FISH+, approximately 16% of gastric cancers are considered Her2 positive, affecting mainly tumor regions with intestinal (gland forming) type carcinoma. In contrast to breast cancer, up to one-third of gastric cancers show a heterogeneous Her2 status both at IHC and ISH levels which favors bright field ISH over FISH.