HER2 by immunohistochemistry and FISH in Breast Cancer: Impact of the 2007 ASCO/CAP criteria

Kurt A. Schalper, Sudha Kumar, Pei Hui, David L. Rimm, and Peter Gershkovich (2013) 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. Archives of Pathology & Laboratory Medicine In-Press.

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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

Kurt A. Schalper , MD, PhD; Sudha Kumar , BE, MOT; Pei Hui , MD, PhD; David L. Rimm , MD, PhD; Peter Gershkovich , MD, MHA

From the Department of Pathology, Yale School of Medicine, New Haven, Connecticut (Drs Schalper, Kumar, Hui, Rimm, and Gershkovich) and Servicio de Anatomia Patologica, Clinica Alemana de Santiago, Chile (Dr Schalper).

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 between 2002 and 2006 were scored by using original US Food and Drug Administration criteria (N = 1138) and those 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.