A Retrospective Population-based Comparison of HER2 Immunohistochemistry and Fluorescence in Situ Hybridization in Breast Carcinomas: Impact of 2007 American Society of Clinical Oncology/College of American Pathologists Criteria

Context: In 2007 the American Society of Clinical Oncology/College of American Pathologists made new recommendations for HER2 testing and redefined HER2 positivity.

Objective: To analyze results from simultaneous HER2 testing with immunohistochemistry and fluorescence in situ hybridization (FISH) in 2590 invasive breast carcinomas between 2002 and 2010, using 2 scoring systems.

Design: Cases from between 2002 and 2006 were scored by using original US Food and Drug Administration criteria (N = 1138) and those from between 2007 and 2010 were evaluated according to American Society of Clinical Oncology/College of American Pathologists criteria (N = 1452). Concordance between testing methods and clinicopathologic associations were determined.

Results: Overall concordance between immunohistochemistry/FISH in the 9-year period was 96.2% (κ = 0.82), and positive concordance was lower. After 2007, the proportion of HER2/neu-positive and HER2/neu-negative cases was not significantly changed when using immunohistochemistry (10.5% versus 8.9%, P = .22 and 69.4% versus 63%, P = .13, respectively), but the number of equivocal cases was higher (19.9% versus 28%, P < .001). While the proportion of negative cases by FISH remained unchanged after 2007 (86.5% versus 88.2%, P = .76), the number of positive cases was lower (13.4% versus 9.2%, P < .001). In addition, 38 cases (2.6%) were FISH equivocal, 16 of which were also equivocal by immunohistochemistry. Overall, immunohistochemistry/FISH concordance was 95.9% between 2002 and 2006 (κ = 0.82) and 96.4% after 2007 (κ = 0.82). However, an approximately 13% lower positive assay concordance was noted in the last period.

Conclusions: Application of American Society of Clinical Oncology/College of American Pathologists recommendations is associated with comparable overall immunohistochemistry/FISH concordance, reduced positive concordance, and increased equivocal results.