A Modified HER2 Image Analysis Algorithm with ASCO/CAP Criteria Has High Concordance with FISH
Douglas M Minot, Jesse S Voss, Benjamin R Kipp, Ahmet Dogan, Rhett P Ketterling, Amy M Plagge, Taofic Mounajjed, Amy C Clayton. Mayo Clinic, Rochester, MN
Background: Pathological assessment of the HER2 protein is a key biomarker to determine trastuzumab eligibility in patients with breast cancer. Recent advancements in image analysis (IA) allow for HER2 scores to be calculated based on guideline recommendations (i.e. ASCO/CAP). In this validation study, we compared results from an FDA-cleared IA algorithm using the Ventana Pathway HER2 stain (Ventana Medical Systems, Tucson, AZ), as well as a modified HER2 IA algorithm using the FDA and ASCO/CAP staining percentage cutoffs.
Design: Slides from 142 breast cancer specimens were analyzed by HER2 IHC and FISH (PathVysion, Abbott Molecular Inc. Des Plaines, IL). These slides were analyzed using the Aperio digital pathology system (Aperio, Vista, CA). The test set (n=58) was analyzed using 2 different analysis techniques: 1)a method representing 6 areas of high, moderate and low intensity staining and 2)a whole tumor tracing method. Two IA algorithms (FDA-cleared and modified) were used to measure HER2 staining intensity and HER2 positivity (3+) was determined using ASCO/CAP and FDA cutoffs. The validation set (n=84) was analyzed using the technique and algorithm that achieved the highest concordance with FISH during the test set. Precision assessments were performed on a set of 20 previously analyzed cases.
Results: The whole tumor tracing technique with a modified IA algorithm using the ASCO/CAP cutoff had the highest accuracy when compared to FISH (100%; 58/58) (Table 1) using the test set. This method also demonstrated very high accuracy (99%; 83/84) (Table 2) and precision (95%; 19/20) for both inter- and intraobserver measurements in the validation set. In addition, 10 cases converted from HER2 IHC (2+) to HER2 (3+) that were all FISH amplified and 15 cases were downgraded from HER2 equivocal (2+) to HER2 negative with one case being FISH amplified.
|6 area method (FDA -cleared)||53/58 (91)|
|6 area method (modified)||56/58 (97)|
|Whole tumor trace (FDA -cleared)||56/58 (97)|
|Whole tumor trace (modified)||57/58 (98)|
|Whole tumor trace (modified and ASCO/CAP cutoffs)||58/58 (100)|