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:
Notes: Article -- Export Date: 2 July 2018 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Dean Bajorin
    413 Bajorin
  2. Guido Dalbagni
    251 Dalbagni
  3. Sherri M Donat
    135 Donat
  4. David Solit
    435 Solit
  5. Satish K Tickoo
    369 Tickoo
  6. Anuradha Gopalan
    274 Gopalan
  7. Gopakumar Vasudeva Iyer
    126 Iyer
  8. Yingbei Chen
    221 Chen
  9. Bernard Bochner
    324 Bochner
  10. Samson W Fine
    316 Fine
  11. Victor Reuter
    913 Reuter
  12. Harry W Herr
    407 Herr
  13. Hongying Huang
    12 Huang
  14. Jonathan Eric Rosenberg
    225 Rosenberg
  15. Byron Hing Lung Lee
    14 Lee