PMID- 29564742 OWN - NLM STAT- MEDLINE DCOM- 20190306 LR - 20190306 IS - 1573-7217 (Electronic) IS - 0167-6806 (Print) IS - 0167-6806 (Linking) VI - 170 IP - 2 DP - 2018 Jul TI - Immunohistochemistry and alternative FISH testing in breast cancer with HER2 equivocal amplification. PG - 321-328 LID - 10.1007/s10549-018-4755-5 [doi] AB - PURPOSE: While HER2 testing is well established in directing appropriate treatment for breast cancer, a small percentage of cases show equivocal results by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Alternative probes may be used in equivocal cases. We present a single community-based institution's experience in further evaluating these cases. PATIENTS AND METHODS: Between 2014 and 2016, 4255 samples were submitted for HER2 amplification testing by alternative probes, TP53, RAI1, and RARA. Of the patients tested by FISH, 505/3908 (12.9%) also had IHC data. RESULTS: Most (73.9%) FISH equivocal cases remained equivocal after IHC testing. However, 50.5% of equivocal cases were classified as HER2 amplified by alternative probes. Most cases were positive by more than one probe: 78% of positive cases by RAI1 and 73.9% by TP53. There was a significant difference between IHC and FISH alternative testing (p < 0.0001) among the equivocal cases by conventional FISH testing, 44% of IHC negative cases became positive while 36% of the positive IHC cases became negative by alternative FISH testing. Available data showed that 41% of patients were treated with palbociclib and were positive by alternative FISH. CONCLUSION: The prevalence of double HER2 equivocal cases and the discrepancy between IHC and alternative FISH testing suggest that FISH alternative testing using both RAI1 and TP53 probes is necessary for conclusive classification. Because almost half of FISH equivocal cases converted to HER2 amplified upon alternative testing, clinical studies to determine the benefit of anti-HER2 therapy in these patients are urgently needed. FAU - Agersborg, Sally AU - Agersborg S AD - NeoGenomics Laboratories, Research and Development, 31 Columbia, Aliso Viejo, CA, 92656, USA. FAU - Mixon, Christopher AU - Mixon C AD - NeoGenomics Laboratories, Research and Development, 31 Columbia, Aliso Viejo, CA, 92656, USA. FAU - Nguyen, Thanh AU - Nguyen T AD - NeoGenomics Laboratories, Research and Development, 31 Columbia, Aliso Viejo, CA, 92656, USA. FAU - Aithal, Sramila AU - Aithal S AD - Cancer Treatment Centers of America, Philadelphia, PA, USA. FAU - Sudarsanam, Sucha AU - Sudarsanam S AD - NeoGenomics Laboratories, Research and Development, 31 Columbia, Aliso Viejo, CA, 92656, USA. FAU - Blocker, Forrest AU - Blocker F AD - NeoGenomics Laboratories, Research and Development, 31 Columbia, Aliso Viejo, CA, 92656, USA. FAU - Weiss, Lawrence AU - Weiss L AD - NeoGenomics Laboratories, Research and Development, 31 Columbia, Aliso Viejo, CA, 92656, USA. FAU - Gasparini, Robert AU - Gasparini R AD - NeoGenomics Laboratories, Research and Development, 31 Columbia, Aliso Viejo, CA, 92656, USA. FAU - Jiang, Shiping AU - Jiang S AD - NeoGenomics Laboratories, Research and Development, 31 Columbia, Aliso Viejo, CA, 92656, USA. FAU - Chen, Wayne AU - Chen W AD - NeoGenomics Laboratories, Research and Development, 31 Columbia, Aliso Viejo, CA, 92656, USA. FAU - Hess, Gregory AU - Hess G AD - Symphony Health, Conshohocken, PA, USA. FAU - Albitar, Maher AU - Albitar M AUID- ORCID: 0000-0001-7661-9537 AD - NeoGenomics Laboratories, Research and Development, 31 Columbia, Aliso Viejo, CA, 92656, USA. maheralbitar@gmail.com. LA - eng PT - Journal Article DEP - 20180322 PL - Netherlands TA - Breast Cancer Res Treat JT - Breast cancer research and treatment JID - 8111104 RN - 0 (Biomarkers, Tumor) RN - 0 (Receptors, Estrogen) RN - 0 (Receptors, Progesterone) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - *Biomarkers, Tumor MH - Breast Neoplasms/*genetics/*metabolism/pathology MH - Female MH - Gene Amplification MH - Humans MH - *Immunohistochemistry MH - *In Situ Hybridization, Fluorescence MH - Receptor, ErbB-2/*genetics/*metabolism MH - Receptors, Estrogen/metabolism MH - Receptors, Progesterone/metabolism PMC - PMC5999182 OTO - NOTNLM OT - Breast cancer OT - Equivocal OT - FISH OT - HER2 OT - IHC COIS- Sally Agersborg, Christopher Mixon, Thanh Nguyen, Sucha Sudarsanam, Forrest Blocker, Lawrence Weiss, Bob Gasparini, Shiping Jiang, Wayne Chen, and Maher Albitar are employed by NeoGenomics, an oncology reference laboratory. Gregory Hess is employed by Symphony Health, a medical data analytics company. EDAT- 2018/03/23 06:00 MHDA- 2019/03/07 06:00 PMCR- 2018/03/22 CRDT- 2018/03/23 06:00 PHST- 2017/11/15 00:00 [received] PHST- 2018/03/13 00:00 [accepted] PHST- 2018/03/23 06:00 [pubmed] PHST- 2019/03/07 06:00 [medline] PHST- 2018/03/23 06:00 [entrez] PHST- 2018/03/22 00:00 [pmc-release] AID - 10.1007/s10549-018-4755-5 [pii] AID - 4755 [pii] AID - 10.1007/s10549-018-4755-5 [doi] PST - ppublish SO - Breast Cancer Res Treat. 2018 Jul;170(2):321-328. doi: 10.1007/s10549-018-4755-5. Epub 2018 Mar 22.