Article

Assessment of a HER2 scoring system for gastric cancer: results from a validation study

Institute of Pathology, Klinikum Kassel, Kassel, Germany.
Histopathology (Impact Factor: 3.3). 07/2008; 52(7):797-805. DOI: 10.1111/j.1365-2559.2008.03028.x
Source: PubMed

ABSTRACT Human epidermal growth factor receptor 2 (HER2) overexpression/amplification is implicated in the development of various solid tumour types. Validated methods and scoring systems for evaluating HER2 status exist in breast cancer, but not in gastric cancer. The aim was to establish a HER2 scoring system for gastric cancer to identify suitable patients for enrollment in a trial of trastuzumab (Herceptin) in advanced metastatic gastric cancer.
Formalin-fixed paraffin-embedded gastric cancer samples were tested for HER2 status using the fluorescence in situ hybridization (FISH) pharmDxt kit (Dako Denmark A/S). Immunohistochemistry (IHC) was performed using the HercepTest (Dako). Concordance between FISH and IHC was 93.5% in 168 evaluable samples. Eleven samples were scored as FISH+ but IHC- or equivocal.
IHC/FISH discrepancies were attributed to basolateral membranous immunoreactivity of glandular cells resulting in incomplete membranous reactivity and/or a higher rate of tumour heterogeneity in gastric cancer compared with breast cancer. With modifications to the IHC scoring system, the HercepTest is considered valid for the identification of HER2+ gastric tumours for this clinical trial. Correlation of HER2 scores with clinical outcomes will be needed to determine which patients might benefit from trastuzumab therapy.

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