Molecular Pathology Laboratory Network

 As for many predictive assays, technical considerations and interpretive guidelines are critical. The ToGA trial demonstrated superiority for immunohistochemistry over the FISH assay in predicting response to drug. In gastric cancer, immunohistochemistry is more predictive than FISH in selection of patients for Herceptin therapy. Based on the ToGA data, only immunohistochemical 2+ gastric cancers should be reflexed to HER2 FISH testing. Herceptin benefit was essentially limited to immunohistochemically 3+ gastric cancers or IHC2+ and FISH+ cancers.

Immunohistochemical scoring criteria are different for gastric cancer. In gastric cancers, positive membranous-pattern staining can be basolateral, lateral, or complete; but unlike breast cancer, does not have to be complete. In gastric cancer biopsies, an allowable tumor focus should have at least five stained cells. In surgical resection specimens, >10% of tumor cells must be stained. In the ToGA trial, strict application of breast cancer interpretation guidelines would have resulted in a 50% false-negative rate for scoring gastric cancer.

The ToGA trial utilized the DAKO Herceptest immunohistochemical stain. However, two large comparison studies have shown high correlation between this system and the Ventanna PATHWAY system, both FDA approved for breast cancer testing. Without strict attention to gastric-specific interpretation guidelines, one could falsely interpret granular pattern staining of small cellular groups, positive staining of benign intestinal metaplasia, or diffuse cytoplasmic tumor cell staining as HER2 positivity.     

HER2 Gastric by Immunohistochemsitry

HER2 Gastric by FISH 

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