PMID- 35623464 OWN - NLM STAT- MEDLINE DCOM- 20220812 LR - 20221018 IS - 1532-8392 (Electronic) IS - 0046-8177 (Linking) VI - 126 DP - 2022 Aug TI - Digital imaging correlation of immunohistochemistry and fluorescence in situ hybridization in breast carcinoma cases with HER2 genetic heterogeneity. PG - 129-135 LID - S0046-8177(22)00137-X [pii] LID - 10.1016/j.humpath.2022.05.011 [doi] AB - Genetic heterogeneity (GH) is a rare but important event in the evaluation of HER2 amplification status. We investigated whether HER2 fluorescence in situ hybridization (FISH) GH correlated with increased protein expression by immunohistochemistry (IHC) and/or morphologic features using image analyses. Retrospective search of HER2 FISH GH cases 2016-2020 was performed. Cases with both FISH and IHC slides available were considered eligible and were digitally imaged. Additional demographic, histological, and treatment information was compiled from pathology and medical records when available. Overall, 11 of 15 cases (73.3%) had HER2 FISH GH that matched to areas of HER2 overexpression or focally different morphology. Nine cases with areas of gene amplification overlapped with <10% of intense circumferential protein expression ("Mini 3+"), and 1 case with focal micropapillary features. Clinical information was available on 6 patients (40%), all were alive with no evidence of disease (mean follow-up 30.5 months; range, 12-65 months). One patient with GH and a lymph node metastasis showed nonamplified population in the nodal tumor. GH, when defined as discrete clusters of amplified cells following 2013 ASCO/CAP guidelines, even when less than 10% of the tumor cells, frequently has morphologic correlates such as focal intense protein overexpression or micropapillary morphology. Clinical significance of these focal gene amplification and protein overexpression needs to be further investigated. CI - Copyright (c) 2022. Published by Elsevier Inc. FAU - Wilcock, Diane M AU - Wilcock DM AD - ARUP Laboratories, 500 Chipeta Way, Salt Lake City, UT 84108, USA. FAU - Sirohi, Deepika AU - Sirohi D AD - ARUP Laboratories, 500 Chipeta Way, Salt Lake City, UT 84108, USA; University of Utah, Department of Pathology, Huntsman Cancer Institute, 2000 Circle of Hope, Room 3100, Salt Lake City, UT 84124, USA. FAU - Coleman, Joshua F AU - Coleman JF AD - ARUP Laboratories, 500 Chipeta Way, Salt Lake City, UT 84108, USA; University of Utah, Department of Pathology, Huntsman Cancer Institute, 2000 Circle of Hope, Room 3100, Salt Lake City, UT 84124, USA. FAU - Gulbahce, H Evin AU - Gulbahce HE AD - ARUP Laboratories, 500 Chipeta Way, Salt Lake City, UT 84108, USA; University of Utah, Department of Pathology, Huntsman Cancer Institute, 2000 Circle of Hope, Room 3100, Salt Lake City, UT 84124, USA. Electronic address: Evin.Gulbahce@path.utah.edu. LA - eng PT - Journal Article DEP - 20220524 PL - United States TA - Hum Pathol JT - Human pathology JID - 9421547 RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - *Breast Neoplasms/pathology MH - Female MH - Gene Amplification MH - Genetic Heterogeneity MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence/methods MH - *Receptor, ErbB-2/analysis MH - Retrospective Studies OTO - NOTNLM OT - Digital image OT - FISH OT - Genetic heterogeneity OT - HER2 OT - Micropapillary EDAT- 2022/05/28 06:00 MHDA- 2022/08/13 06:00 CRDT- 2022/05/27 19:24 PHST- 2022/05/05 00:00 [received] PHST- 2022/05/18 00:00 [accepted] PHST- 2022/05/28 06:00 [pubmed] PHST- 2022/08/13 06:00 [medline] PHST- 2022/05/27 19:24 [entrez] AID - S0046-8177(22)00137-X [pii] AID - 10.1016/j.humpath.2022.05.011 [doi] PST - ppublish SO - Hum Pathol. 2022 Aug;126:129-135. doi: 10.1016/j.humpath.2022.05.011. Epub 2022 May 24.