MP48-03 INTRATUMORAL HETEROGENEITY OF ERBB2 AMPLIFICATION AND HER2 EXPRESSION IN MICROPAPILLARY UROTHELIAL CARCINOMA

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology II1 Apr 2017MP48-03 INTRATUMORAL HETEROGENEITY OF ERBB2 AMPLIFICATION AND HER2 EXPRESSION IN MICROPAPILLARY UROTHELIAL CARCINOMA Sumit Isharwal, Hongying Huang, Gouri Nanjangud, François Audenet, Ying-Bei Chen, Anuradha Gopalan, Samson Fine, Satish Tickoo, Gopakumar Iyer, Jonathan Rosenberg, Dean Bajorin, Harry Herr, Machele Donat, Guido Dalbagni, Bernard Bochner, David Solit, Victor Reuter, and Hikmat Al-Ahmadie Sumit IsharwalSumit Isharwal More articles by this author , Hongying HuangHongying Huang More articles by this author , Gouri NanjangudGouri Nanjangud More articles by this author , François AudenetFrançois Audenet More articles by this author , Ying-Bei ChenYing-Bei Chen More articles by this author , Anuradha GopalanAnuradha Gopalan More articles by this author , Samson FineSamson Fine More articles by this author , Satish TickooSatish Tickoo More articles by this author , Gopakumar IyerGopakumar Iyer More articles by this author , Jonathan RosenbergJonathan Rosenberg More articles by this author , Dean BajorinDean Bajorin More articles by this author , Harry HerrHarry Herr More articles by this author , Machele DonatMachele Donat More articles by this author , Guido DalbagniGuido Dalbagni More articles by this author , Bernard BochnerBernard Bochner More articles by this author , David SolitDavid Solit More articles by this author , Victor ReuterVictor Reuter More articles by this author , and Hikmat Al-AhmadieHikmat Al-Ahmadie More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1484AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Micropapillary urothelial carcinoma (MPUC) is a rare but an aggressive variant of urothelial carcinoma. Histologically, most of these tumors are associated with variable amounts of ″not otherwise specified (NOS)″ urothelial carcinoma. MPUC has been previously shown to be associated with ERBB2 amplification and HER2 protein overexpression. However, the status and distribution of these findings within MP and NOS components of MPUC have not been addressed. Therefore, we evaluated the ERBB2/HER2 expression in MP and NOS components by FISH and IHC. METHODS We identified 44 cases of MPUC that had tissue available for FISH and IHC at our institute, of which an NOS component sufficient for both FISH and IHC was identified in 37 cases. We followed the updated ASCO/CAP Guidelines for breast cancer and as such amplification was defined by a HER2/CEP17 ratio of ≥2.0 or > 6 copies of the gene and HER2 overexpression was considered with IHC scores of 2+ and 3+. RESULTS In urothelial tumors with both MP and NOS components (n = 37), ERBB2 amplification in MP and NOS components was present in 25 and 16 cases respectively. ERBB2 amplification was significantly higher in the MP component compared to NOS component within the same tumor (67.57% vs. 43.24%, p = 0.049). HER2 overexpression in MP and NOS components was present in 25 and 13 cases respectively. HER2 overexpression was significantly higher in the MP component compared to NOS component within the same tumor (67.56% vs. 35.13%, p = 0.012). In addition, ERBB2 amplification strongly correlated with HER2 overexpression in both MP (rho = 0.65, p<0.001) and NOS (rho = 0.74, p<0.001) components. In this cohort (n = 44), tumor stage and lymph node status were significant predictors for overall survival (p = 0.01, <0.001 respectively). However, ERBB2 amplification and HER2 overexpression in MP component were not associated with patients′ survival outcome (p=1.00, 0.75 respectively). CONCLUSIONS The majority of MPUC is associated with ERBB2 amplification and HER2 overexpression. In MPUC, ERBB2 amplification and HER2 overexpression were preferentially but not exclusively identified in MP component compared to NOS component. Our findings provide evidence for intratumoral heterogeneity of ERBB2 amplification and HER2 expression in MPUC. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e637-e638 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Sumit Isharwal More articles by this author Hongying Huang More articles by this author Gouri Nanjangud More articles by this author François Audenet More articles by this author Ying-Bei Chen More articles by this author Anuradha Gopalan More articles by this author Samson Fine More articles by this author Satish Tickoo More articles by this author Gopakumar Iyer More articles by this author Jonathan Rosenberg More articles by this author Dean Bajorin More articles by this author Harry Herr More articles by this author Machele Donat More articles by this author Guido Dalbagni More articles by this author Bernard Bochner More articles by this author David Solit More articles by this author Victor Reuter More articles by this author Hikmat Al-Ahmadie More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...