[2145] 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 HER 2 Score Using Gastric Criteria, Breast Criteria and Image Analysis

	Consensus HER2 Score
Scoring Method	0	1+	2+	3+	Total
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

*Percentage of cases FISH positive in parentheses


Conclusions: Fewer cases were undercalled using gastric HER2 IHC scoring criteria or image analysis while one case was overcalled, when compared to standard breast scoring guidelines. Based on our validation study, the modification made to the scoring criteria to account for incomplete reactive membranes and tumor heterogeneity seems justified. In addition, image analysis could yield fewer equivocal cases that would be reflexed to FISH.
Category: Techniques

Monday, March 19, 2012 1:00 PM

Poster Session II # 309, Monday Afternoon