HER2 FISH concordance in breast cancer patients with both cytology and surgical pathology specimens

Fluorescence in Situ Hybridization (FISH) for Human Epidermal Growth Factor Receptor 2 (HER2) is traditionally performed on histologic specimens; there are no guidelines for validation of HER2 testing on cytology specimens. Our aim was to correlate HER2 FISH results on cytologic and histologic specimens.

A retrospective search was conducted to identify breast carcinomas with HER2 FISH testing on both cytologic and histologic specimens. Results were interpreted using updated 2013 ASCO/CAP guidelines.

54 women with HER2 FISH results on both cytologic and histologic specimens were identified. HER2 FISH was performed on 26 formalin-fixed thrombin clot cell blocks, 6 Cellient (Hologic, Inc., Bedford, MA) cell blocks and 22 ThinPrep slides, and was negative in 43 (87%), positive in 8 (15%), and equivocal in 3 (5%) cases. Of 43 negative cytology cases, the histologic specimen was also negative in 40 (93%). Of 8 positive cytology cases, the histologic specimen was positive in 5 (63%). Overall, 48 of 54 cases (89%) had a concordant result. In patients with a discordant result, the average interval between HER2 FISH testing was 7 years. Three of 6 discordant cases showed HER2 genetic heterogeneity. Five patients received adjuvant chemotherapy, 2 received endocrine therapy, and 1 received trastuzumab.

FISH is reliable for determining HER2 status in cytopathology specimens. Discordant results between cytologic and surgical specimens are uncommon; possible explanations include genetic heterogeneity or inherent molecular changes associated with disease progression and therapies that occur between testing of the primary carcinoma and the metastasis.