Clinicopathologic Characteristics of HER2 FISH Ambiguous Breast Cancer at a Single Institution
Michael R Clay, Kristin C Jensen. Stanford Hospital and Clinics, Stanford, CA; Veterans Affairs, Palo Alto Health Care System, Palo Alto, CA
Background: The typical algorithm for HER2 testing is immunohistochemistry (IHC) followed by reflex HER2 fluorescence in situ hybridization (FISH) for HER2 IHC ambiguous (2+) cases. At our institution, HER2 FISH testing is initially performed as part of routine breast cancer testing, with HER2 FISH ambiguous (HER2:CEP17 ratio 1.8-2.2) cases reflexed to HER2 IHC. This provides a unique dataset for lesions that may not routinely undergo FISH testing. The clinicopathologic characteristics of HER2 FISH ambiguous cases are described.
Design: The electronic pathology database in our institution was searched for HER2 FISH ambiguous cases from 2007 to July 2011. All breast pathology reports were reviewed, and retrospective clinical charts were examined for details on treatment and outcome.
Results: Sixty-four cases from 59 patients (all female, age range 23-90, mean age 56) were reported as HER2 ambiguous during this period. Reflex HER2 IHC testing was performed on 55 cases, of which 25 were HER2 IHC negative (0-1+), 15 were HER2 IHC ambiguous (2+), and 15 were HER2 IHC positive (3+). Thirty-three cases had associated ductal carcinoma in situ. Of the HER2 FISH ambiguous patients with available clinical records, 42 were considered for anti-HER2 therapy (28 patients with FISH ratios < 2.0 and 14 patients with FISH ratios 2.0-2.2) and of these 11 pursued anti-HER2 treatment (8 with HER2 IHC 3+, 2 with HER2 IHC negative but FISH ratios greater than 2, and 1 with HER2 IHC 2+ and FISH ratio 1.91).
Conclusions: Reflex HER2 IHC testing after initial HER2 FISH testing provides definitive HER2 status information in a majority of cases (73%). However, a substantial percentage (27%) of HER2 FISH ambiguous cases are also HER2 IHC ambiguous, suggesting an intermediate HER2 biology. Most HER2 FISH ambiguous who received anti-HER2 therapy (91%) were either HER2 IHC 3+ or FISH ratio 2 or greater.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 22, Monday Morning