BACKGROUND: : The typical algorithm for human epidermal growth factor-2 (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 to 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 December 2011. Review of clinical and pathologic characteristics was performed. RESULTS: : Sixty cases from 60 patients were reported as HER2 FISH ambiguous. Reflex HER2 IHC testing was performed on all 60 cases, of which 26 were HER2 IHC negative (0 to 1+), 18 were HER2 IHC ambiguous (2+), and 16 were HER2 IHC positive (3+). Of the 46 HER2 FISH-ambiguous patients with available clinical records, 13 (32%) pursued anti-HER2 treatment (10 IHC 3+, 1 IHC 2+, 2 IHC 0 to 1+). All were grade II or III ductal carcinomas, with 1 grade III metaplastic carcinoma. CONCLUSIONS: : Reflex HER2 IHC testing after initially ambiguous HER2 FISH testing provides definitive HER2 status in a majority of cases (70%). However, a substantial percentage (30%) of HER2 FISH-ambiguous cases is also HER2 IHC ambiguous, suggesting an intermediate HER2 biology. Most HER2 FISH-ambiguous patients who received trastuzumab were HER2 IHC 3+, grade III, and had associated high-grade ductal carcinoma in situ. Although not statistically significant and with only minimal follow-up, no recurrences have occurred in those patients treated with trastuzumab (P=0.5754).
BACKGROUND: : The typical algorithm for human epidermal growth factor-2 (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 to 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 December 2011. Review of clinical and pathologic characteristics was performed. RESULTS: : Sixty cases from 60 patients were reported as HER2 FISH ambiguous. Reflex HER2 IHC testing was performed on all 60 cases, of which 26 were HER2 IHC negative (0 to 1+), 18 were HER2 IHC ambiguous (2+), and 16 were HER2 IHC positive (3+). Of the 46 HER2 FISH-ambiguous patients with available clinical records, 13 (32%) pursued anti-HER2 treatment (10 IHC 3+, 1 IHC 2+, 2 IHC 0 to 1+). All were grade II or III ductal carcinomas, with 1 grade III metaplastic carcinoma. CONCLUSIONS: : Reflex HER2 IHC testing after initially ambiguous HER2 FISH testing provides definitive HER2 status in a majority of cases (70%). However, a substantial percentage (30%) of HER2 FISH-ambiguous cases is also HER2 IHC ambiguous, suggesting an intermediate HER2 biology. Most HER2 FISH-ambiguous patients who received trastuzumab were HER2 IHC 3+, grade III, and had associated high-grade ductal carcinoma in situ. Although not statistically significant and with only minimal follow-up, no recurrences have occurred in those patients treated with trastuzumab (P=0.5754).
Authors: David D Stenehjem; Minkyoung Yoo; Sudhir K Unni; Mukul Singhal; Hillevi Bauer; Kim Saverno; Cheng Quah; Anthony Masaquel; Diana I Brixner Journal: Breast Cancer (Dove Med Press) Date: 2014-10-29
Authors: Chantal C H J Kuijpers; Cathy B Moelans; Henk-Jan van Slooten; Anja Horstman; John W J Hinrichs; Shaimaa Al-Janabi; Paul J van Diest; Mehdi Jiwa Journal: PLoS One Date: 2013-12-04 Impact factor: 3.240