Synapse - Intratumoral heterogeneity of ERBB2 amplification and HER2 expression in micropapillary urothelial carcinoma

Intratumoral heterogeneity of ERBB2 amplification and HER2 expression in micropapillary urothelial carcinoma Journal Article

Authors:	Isharwal, S.; Huang, H.; Nanjangud, G.; Audenet, F.; Chen, Y. B.; Gopalan, A.; Fine, S. W.; Tickoo, S. K.; Lee, B. H.; Iyer, G.; Chadalavada, K.; Rosenberg, J. E.; Bajorin, D. F.; Herr, H. W.; Donat, S. M.; Dalbagni, G.; Bochner, B. H.; Solit, D. B.; Reuter, V. E.; Al-Ahmadie, H. A.
Article Title:	Intratumoral heterogeneity of ERBB2 amplification and HER2 expression in micropapillary urothelial carcinoma
Abstract:	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 (ρ = 0.59, P <.001) and NOS (ρ = 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. © 2018 Elsevier Inc.
Keywords:	immunohistochemistry; clinical article; controlled study; overall survival; histopathology; cancer patient; gene overexpression; gene amplification; gene expression; epidermal growth factor receptor 2; cell heterogeneity; fluorescence in situ hybridization; scoring system; tumor growth; transitional cell carcinoma; tumor classification; predictive value; correlational study; diagnostic test accuracy study; intratumoral heterogeneity; human; article; micropapillary urothelial carcinoma; human epidermal growth factor receptor-2 (her2, erbb2)
Journal Title:	Human Pathology
Volume:	77
ISSN:	0046-8177
Publisher:	Elsevier Inc.
Date Published:	2018-07-01
Start Page:	63
End Page:	69
Language:	English
DOI:	10.1016/j.humpath.2018.03.015
PROVIDER:	scopus
PMCID:	PMC6019182
PUBMED:	29601842
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85047606713&doi=10.1016%2fj.humpath.2018.03.015&partnerID=40&md5=7e3d337954ba0b3ca11603704e3fbdba
Notes:	Article -- Export Date: 2 July 2018 -- Source: Scopus