Nectin-4 is frequently expressed in primary salivary gland cancer and corresponding lymph node metastases and represents an important treatment-related biomarker

Clin Exp Metastasis. 2023 Oct;40(5):395-405. doi: 10.1007/s10585-023-10222-w. Epub 2023 Jul 22.


Many locally advanced and metastatic salivary gland carcinomas (SGC) lack therapeutic targets. Enfortumab vedotin, an antibody-drug conjugate binding to Nectin-4, recently gained FDA approval for third-line urothelial carcinoma. Therefore, the aim of this study was to assess the expression of Nectin-4 in primary SGC and corresponding lymph node metastases and to correlate it with clinicopathological data. Immunohistochemical staining for Nectin-4 was performed for patients who had undergone surgery with curative intent for primary SGC of the parotid or submandibular gland in a tertiary referral center between 1990 and 2019. One hundred twenty-two primary SGC and twenty corresponding lymph node metastases were included. Nectin-4 was expressed in 80.3% of primary SGC with a mean Histo(H-)score of 61.2 and in 90.0% of lymph node metastases with a mean H-score of 75.6. A moderate or high Nectin-4 expression was found in 25.9% of salivary duct carcinomas (SaDu) and in 30.7% of adenoid cystic carcinomas (ACC). SaDu patients with a lower T-stage (p = 0.04), no loco-regional lymph node metastases (p = 0.049), no vascular invasion (p = 0.04), and no perineural spread (p = 0.03) showed a significantly higher mean Nectin-4 H-score. There was a statistical tendency towards a more favorable disease-free survival among SaDu patients with a higher Nectin-4 expression (p = 0.09). Nectin-4 is expressed in SGC and therefore represents a potential therapeutic target, especially in entities with a high rate of local recurrence and metastatic spread such as SaDu and ACC.

Keywords: Enfortumab vedotin; Head and neck cancer; Immunohistochemistry; Nectin-4; Prognosis; Salivary duct carcinoma; Salivary gland neoplasm; Targeted therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Carcinoma, Transitional Cell*
  • Cell Adhesion Molecules
  • Humans
  • Lymphatic Metastasis
  • Nectins
  • Salivary Gland Neoplasms* / drug therapy
  • Urinary Bladder Neoplasms*


  • Nectins
  • Biomarkers
  • Cell Adhesion Molecules