HER2 gene amplification occurs frequently in the micropapillary variant of urothelial carcinoma: Analysis by dual-color in situ hybridization

Christina B. Ching, Mahul B. Amin, Raymond R. Tubbs, Paul Elson, Eric Platt, Robert Dreicer, Amr Fergany, Donna E. Hansel

Research output: Contribution to journalArticlepeer-review

69 Scopus citations


Human epidermal growth factor receptor-2 (HER2) is a well-recognized growth-promoting factor in cancer, although its application to urothelial carcinoma has been limited because of a low frequency of gene amplification. We evaluated HER2 protein expression and gene amplification in micropapillary carcinoma, a rare but highly aggressive variant of urothelial carcinoma by dual-color in situ hybridization. Gene amplification was defined by a HER2:CHR17 ratio of 2.2; low and high levels of amplification were further defined as 2.5 and 2.5, respectively. Immunohistochemistry was used to determine HER2 protein expression using the American Society of Clinical Oncology/College of American Pathologists Guidelines of HER2 staining. Protein expression, gene amplification, and chromosome 17 aneusomy were compared by Jonchkeere-Terpstra and Cochran-Armitage trend tests. In all, 19 of the 20 micropapillary carcinoma samples yielded usable dual-color in situ hybridization and immunohistochemistry results for evaluation. Overall, 68% (n13) demonstrated HER2 protein expression of 2 to 3 staining. Gene amplification was present in 42% of samples (n8), with 100% correlation with 2 and 3 protein expression. Gene amplification and protein expression were significantly associated (P0.01). Overall, 53% of samples (n10) had aneusomy of chromosome 17. Chromosome 17 aneusomy was present in approximately half of the samples evaluated, suggesting inherent genomic instability in this variant of urothelial carcinoma. However, increased HER2:CHR17 ratios demonstrate increased HER2 expression due to amplification in the majority of micropapillary carcinomas. These results suggest that HER2-targeted therapy may be successful on the genomic level in patients with this disease.

Original languageEnglish (US)
Pages (from-to)1111-1119
Number of pages9
JournalModern Pathology
Issue number8
StatePublished - Aug 2011
Externally publishedYes


  • chromogenic in situ hybridization
  • dual ISH
  • gene amplification
  • human epidermal growth factor receptor-2 (HER2) (ERBB2)
  • micropapillary carcinoma
  • silver in situ hybridization
  • urothelial carcinomaX

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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