Validation of HER2 Immunohistochemical Stain Gastric Scoring Criteria for Esophagogastric Cancer
Douglas M Minot, Harry H Yoon, Jesse S Voss, Michael R Henry, Jun Zhang, Tsung-Teh Wu, Rhett P Ketterling, Amy C Clayton. Mayo Clinic, Rochester, MN
Background: New scoring guidelines have been developed and published for the interpretation of HER2 immunohistochemistry (IHC) expression in esophagogastric cancer specimens due to recognized differences in cell morphology and tumor heterogeneity. The purpose of this study is to assess the accuracy of these guidelines performed manually in comparison to image analysis (Aperio) and the established CAP/ASCO HER2 breast scoring guidelines using fluorescence in situ hybridization (FISH) as a gold standard.
Design: Ninety specimens were chosen for IHC and FISH analysis (42 esophageal biopsies with 5 matched resections, and 33 gastric biopsies with 10 matched resections). A total of 18 cases were excluded (15 insufficient for FISH analyses, 2 with insufficient tumor present in the block, and 1 equivocal FISH interpretation). Three pathologists reached a consensus interpretation on all cases based on gastric HER2 IHC guidelines and breast HER2 IHC guidelines. Image analysis was performed using the Aperio imaging system (Aperio Technologies, Vista, CA) on areas of highest stain intensity using default instrument cut-offs.
Results: Data from the 72 cases are shown (Table). Using the gastric criteria, there were no false negative cases (IHC negative [0 and 1+]/FISH positive) and 1 false positive case (IHC positive [3+]/FISH negative). Interpretations based on breast criteria yielded 2 false negative cases and 0 false positive cases. There were no false negative and one false positive case using image analysis, while having the fewest 2+ cases (n=7) resulting in the highest percentage of 2+ IHC cases (57%) being FISH positive. There was complete concordance (100%) for all IHC analysis methods between the 10 paired biopsy/resection specimens with sufficient tissue for FISH.
|Consensus HER2 Score|
|Gastric IHC Criteria||41 (0)||16 (0)||9 (44)||6 (83)||72|
|Breast IHC Criteria||41 (0)||20 (10)||8 (50)||3 (100)||72|
|IHC Image Analysis||40 (0)||19 (0)||7 (57)||6 (83)||72|