Chromogene in-situhybridisatie voor de terugbetaling van trastuzumab bij gemetastaseerde maagkanker

Abstract

Trastuzumab in metastatic gastric cancer: validation of HER2 chromogenic in situ hybridization In analogy to breast cancer, trastuzumab has recently become reimbursable in Belgium for metastatic gastric cancer with proven HER2 („human epidermal growth factor receptor 2”) gene amplification. This amplification has to be demonstrated by in situ hybridization (ISH), in a specialized laboratory that can guarantee an adequate validation of the procedure. The department of pathology of UZ Leuven (Belgium) selected chromogenic ISH (CISH). The HER2 CISH procedure was optimized, and its repeatability as well as its reproducibility were proven. HER2 CISH was found to be equivalent to HER2 FISH (fluorescence in situ hybridization) on a series of 20 metastatic breast cancers. In addition, the HER2 CISH procedure was tested on a group of 60 metastatic gastric cancers. Several preanalytic variables were evaluated: recent samples, fixed in formalin or Carnoy fixative, were found most suitable. The scoring criteria for HER2 immunohistochemistry (IHC) and CISH compared with those for breast cancer are discussed. A strong correlation in HER2 CISH status (positive or negative) occurred between two independent observers. 20% of the samples displayed HER2 gene amplification. In contrast to recent data from recent literature and probably due to the smaller amount of the series, this percentage remained independent of the histopathologic type of the tumor (diffuse or not diffuse). The associated IHC scores ranged from 0 to 3+, more than half of them presenting an IHC score of 3+. No difference in HER2 CISH status could be demonstrated between different tissue samples of the same tumor and between primary versus metastatic tumor tissue.