HER2 Testing: The Equivocal Category by Immunohistochemistry Should Be Expanded To Include Cases with Any 2+ Staining and Cases with 3+ Staining in <70% Instead of <30% of Tumor Cells To Have High Concordance Rate with FISH.
Thaer Khoury, Dongfeng Tan, Wiam Bshara. Roswell Park Cancer Center, Buffalo; MD anderson Medical Center, Houston
Background: HER2 testing in breast carcinoma identifies patients who are eligible for target therapy with trastuzumab. The ASCO-CAP recommended testing cases with fluorescence in situ hybridization (FISH) if <30% of tumor cells had complete strong membranous staining (3+) by immunohistochemistry (IHC). However, the discordance rate between IHC and FISH is still relatively high and poses a major clinical issue. We re-defined the equivocal (2+) category of HER2 by IHC to increase the concordance rate with FISH.
Design: Cases were scored by Aperio automotaed scoring system that gives percentage of each staining category (from 0 to 3). Cases that have HER2 IHC staining between 2+ (weak to moderate complete) in ≥ 1% of tumor cells and 3+ (complete strong) in < 90% of the tumor cells were tested by FISH. As part of quality assurance, we tested 41 cases with 3+ in ≥90% of tumor cells and 100 cases with 0+ and 1+ staining.
Results: We retrospectively identified 106 cases that met these criteria. In all cases, HER2 was amplified in 18 (17%), borderline in 5 (4.7%) and negative in 83 (78.3%) cases. There were two categories that are not required to be tested by FISH based on ASCO-CAP criteria. The first category, cases with 2+ staining between ≥1% and <10. In this category, there were 15 cases, 2 (13.3%) had HER2 amplification by FISH. The second category, cases with 3+ staining between >30 and <90. In this category, there were 16 cases, 10 (62.5%) were amplified, 5 (31.3%) not amplified and one (6.3%) borderline (table). All cases with 3+ staining in ≥70% had HER2 amplification. IHC and FISH concordance rate in all QA cases was 100%.
Conclusions: In order to increase the concordance rate for HER2 testing between IHC and FISH, the equivocal category should include any 2+ staining and cases with 3+ staining in <70% of tumor cells.
|all cases||106||18 (17)*||5 (4.7)||83 (78.3)|
|IHC 2+ between 1% and 10%||15||2 (13.3)||0 (0)||13 (87.7)|
|IHC 3+ between 30% and 90%||16||10 (62.5)||1 (6.3)||5 (31.3)|