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Expression of nectin-4 in papillary renal cell carcinoma

Stefanie Zschäbitz1, Marie Mikuteit2,3, Christine Stöhr4

  • 1Dept. of Medical Oncology, National Center of Tumor Diseases, University Hospital Heidelberg, 69120, Heidelberg, Germany.

Discover Oncology
|September 22, 2022
PubMed
Abstract

Insights

Nectin-4 is frequently expressed in papillary renal cell carcinoma (pRCC), particularly type 1. While not a general prognostic marker, its abundance suggests Nectin-4 is a promising therapeutic target for pRCC.

Area of Science:

  • Oncology
  • Uro-oncology
  • Molecular Pathology

Background:

  • Nectin-4 promotes tumor growth and vascularization, making it a key target in cancer therapy.
  • Current treatments for renal cell carcinoma (RCC) include tyrosine kinase inhibitors and checkpoint inhibitors.
  • Enfortumab vedotin-ejf (EV) is an antibody-drug conjugate targeting Nectin-4.

Purpose of the Study:

  • To investigate the expression levels of Nectin-4 in a large cohort of papillary renal cell carcinoma (pRCC) specimens.
  • To assess the potential of Nectin-4 as a prognostic marker and therapeutic target in pRCC.

Main Methods:

  • Analysis of tissue samples from 190 patients with pRCC type 1 and 107 patients with pRCC type 2.
  • Immunohistochemistry (IHC) was used to determine Nectin-4 expression.
  • Clinical data including age, gender, grading, TNM stage, and survival rates were analyzed.

Main Results:

  • Nectin-4 was moderately or strongly positive in 48.4% of type 1 pRCC and 36.4% of type 2 pRCC.
  • No significant association was found between Nectin-4 expression and clinicopathological factors (age, gender, grade, stage).
  • Five-year overall survival was higher in Nectin-4 positive type 1 pRCC compared to negative cases (81.3% vs. 67.8%, p=0.042).

Conclusions:

  • Nectin-4 expression is common in pRCC, especially type 1, but does not serve as a general prognostic marker.
  • High Nectin-4 abundance on pRCC specimens identifies it as a potential therapeutic target, for example, with Enfortumab vedotin-ejf.
  • Further clinical trials are necessary to confirm the role of Nectin-4 in pRCC treatment strategies.
Keywords:
Nectin 4Papillary renal cell carcinoma

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