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Targeting HER2 in Urothelial Carcinoma: Why Histologic Subtypes and Divergent Histologies Matter

Emanuele Crupi1, Antonio Cigliola2, Chiara Mercinelli2

  • 1Vita-Salute "San Raffaele" University Hospital, Milan, Italy; Division of Cancer Medicine, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.

Clinical Genitourinary Cancer
|June 8, 2026
PubMed

Insights

HER2 is a relevant target in urothelial carcinoma (UC), but its role varies by subtype. Further research is needed to standardize HER2 testing and guide targeted therapies in UC.

Area of Science:

  • Oncology
  • Genetics
  • Pathology

Background:

  • HER2 is an emerging target in urothelial carcinoma (UC).
  • UC exhibits significant heterogeneity in clinicopathologic features and behavior.
  • Limited data exist on HER2's role across diverse UC histologic subtypes.

Purpose of the Study:

  • To investigate the clinical relevance and therapeutic significance of HER2 in various urothelial carcinoma subtypes.
  • To address uncertainties in HER2 testing and scoring for UC.
  • To inform patient selection for HER2-directed therapies.

Main Methods:

  • Review of existing literature on HER2 alterations in UC.
  • Analysis of retrospective series examining HER2 expression and amplification.
  • Evaluation of assay discordance and scoring criteria.

Main Results:

  • ERBB2 alterations are more frequent in specific UC subtypes like micropapillary carcinoma.
  • Other histologies (plasmacytoid, squamous, sarcomatoid, glandular) show lower and variable HER2 rates.
  • Challenges include small study sizes, assay variability, and lack of standardized scoring.

Conclusions:

  • HER2's biological and therapeutic importance is not uniform across UC histologic subtypes.
  • Standardized HER2 scoring criteria are crucial for UC.
  • Clarifying subtype-specific HER2 status is essential for optimizing HER2-targeted therapies, including antibody-drug conjugates.
Keywords:
Bladder cancerHER2Histologic variantsMicropapillaryUrothelial carcinoma

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