PMID- 29601842 OWN - NLM STAT- MEDLINE DCOM- 20190409 LR - 20190701 IS - 1532-8392 (Electronic) IS - 0046-8177 (Print) IS - 0046-8177 (Linking) VI - 77 DP - 2018 Jul TI - Intratumoral heterogeneity of ERBB2 amplification and HER2 expression in micropapillary urothelial carcinoma. PG - 63-69 LID - S0046-8177(18)30092-3 [pii] LID - 10.1016/j.humpath.2018.03.015 [doi] AB - Micropapillary urothelial carcinoma (MPUC) is a rare but an aggressive variant of urothelial carcinoma. MPUC has been shown to commonly exhibit ERBB2 amplification and HER2 protein overexpression, but the frequency and distribution of these findings within micropapillary (MP) and not otherwise specified (NOS) components of tumors with mixed histology have not been addressed. Therefore, we evaluated ERBB2 amplification and HER2 expression in 43 MPUC cases by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). Of the 35 tumors containing both MP and NOS components, ERBB2 amplification was present in both the MP and NOS components of 12 tumors (34.3%), in only the MP component of 11 tumors (31.4%), and exclusively in the NOS component of 4 tumors (11.4%). HER2 protein overexpression was significantly more commonly present in the MP component compared to the NOS component within the same tumor (68.6% versus 34.3%, P = .012). Overall, there was a moderately positive correlation between HER2 protein expression and ERBB2 amplification in both MP (rho = 0.59, P < .001) and NOS (rho = 0.70, P < .001) components. All MP/NOS areas with IHC score 3+ and none of MP/NOS areas with IHC score 0 were associated with ERBB2 amplification. We conclude that ERBB2 amplification and HER2 overexpression are preferentially but not exclusively identified in the MP component compared to the NOS component within the same tumor. Our findings identify the presence of intratumoral heterogeneity of ERBB2 amplification and HER2 expression in MPUC and provide grounds for further investigation into the mechanisms underlying the development of MPUC. CI - Copyright (c) 2018 Elsevier Inc. All rights reserved. FAU - Isharwal, Sumit AU - Isharwal S AD - Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065. FAU - Huang, Hongying AU - Huang H AD - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065. FAU - Nanjangud, Gouri AU - Nanjangud G AD - Molecular Cytogenetics Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065. FAU - Audenet, Francois AU - Audenet F AD - Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065. FAU - Chen, Ying-Bei AU - Chen YB AD - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065. FAU - Gopalan, Anuradha AU - Gopalan A AD - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065. FAU - Fine, Samson W AU - Fine SW AD - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065. FAU - Tickoo, Satish K AU - Tickoo SK AD - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065. FAU - Lee, Byron H AU - Lee BH AD - Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065. FAU - Iyer, Gopa AU - Iyer G AD - Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065. FAU - Chadalavada, Kalyani AU - Chadalavada K AD - Molecular Cytogenetics Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065. FAU - Rosenberg, Jonathan E AU - Rosenberg JE AD - Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065. FAU - Bajorin, Dean F AU - Bajorin DF AD - Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065. FAU - Herr, Harry W AU - Herr HW AD - Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065. FAU - Donat, S Machele AU - Donat SM AD - Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065. FAU - Dalbagni, Guido AU - Dalbagni G AD - Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065. FAU - Bochner, Bernard H AU - Bochner BH AD - Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065. FAU - Solit, David B AU - Solit DB AD - Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065. FAU - Reuter, Victor E AU - Reuter VE AD - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065. FAU - Al-Ahmadie, Hikmat A AU - Al-Ahmadie HA AD - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065. Electronic address: alahmadh@mskcc.org. LA - eng GR - P30 CA008748/CA/NCI NIH HHS/United States GR - T32 CA082088/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20180327 PL - United States TA - Hum Pathol JT - Human pathology JID - 9421547 RN - EC 2.7.10.1 (ERBB2 protein, human) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Carcinoma, Papillary/*metabolism MH - Carcinoma, Transitional Cell/diagnosis/metabolism MH - Gene Amplification/genetics MH - Gene Expression Regulation, Neoplastic/*genetics MH - Humans MH - Immunohistochemistry/methods MH - Receptor, ErbB-2/*metabolism MH - Urinary Bladder Neoplasms/genetics/*metabolism PMC - PMC6019182 MID - NIHMS955167 OTO - NOTNLM OT - Fluorescence in situ hybridization OT - Human epidermal growth factor receptor-2 (HER2, ERBB2) OT - Immunohistochemistry OT - Intratumoral heterogeneity OT - Micropapillary urothelial carcinoma COIS- Conflict of Interest: None EDAT- 2018/03/31 06:00 MHDA- 2019/04/10 06:00 PMCR- 2019/07/01 CRDT- 2018/03/31 06:00 PHST- 2017/12/02 00:00 [received] PHST- 2018/03/06 00:00 [revised] PHST- 2018/03/19 00:00 [accepted] PHST- 2018/03/31 06:00 [pubmed] PHST- 2019/04/10 06:00 [medline] PHST- 2018/03/31 06:00 [entrez] PHST- 2019/07/01 00:00 [pmc-release] AID - S0046-8177(18)30092-3 [pii] AID - 10.1016/j.humpath.2018.03.015 [doi] PST - ppublish SO - Hum Pathol. 2018 Jul;77:63-69. doi: 10.1016/j.humpath.2018.03.015. Epub 2018 Mar 27.