Immunohistochemical Expression of Claudin-1 and Claudin-4 in Urothelial Carcinoma of the Urinary Bladder

Asian Pac J Cancer Prev. 2024 Feb 1;25(2):637-646. doi: 10.31557/APJCP.2024.25.2.637.

Abstract

Background: In Egypt, bladder cancer occupies the second rankamong reported cancers in men. Claudins are tight junctions that have a critical role in tumor pathogenesis, invasion, progression, and metastasis and currentlyare a focus of interest for targeting therapies.

Objectives: We aimed to evaluatethe immunohistochemical expression of Claudin-1 and Claudin-4 in urinary bladder urothelial carcinoma and investigate the relationshipbetweenthe expressed Claudins with differentclinicopathological parameters.

Methods: Claudin-1 and Claudin-4 immunohistochemical expression was studied in 62 cases of urinary bladder urothelial carcinomas. The cases were classified into two categories; low and high Claudin-1 and Claudin-4 expression.

Results: High Claudin-1 expression was detected in67.7% of the studied urothelial carcinomas while 32.3% showed low expression. Claudin-1 expression was reduced significantly with high tumor grade, non-papillary tumors, muscle invasion, schistosomal infestation, and perineural invasion (p-value < 0.05). Claudin-4 high expression was detected in 82.3% of our cases while low expression was detected in 17.7%. Claudin-4 reduced expression was significantly associated with non-papillary tumors, muscle invasion, advanced T stages, and associated lympho-vascular emboli (P-value < 0.05).

Conclusion: According to the results ofthe present study, the reduced expressions of Claudin-1 and Claudin-4 provide clues concerning the progression of urothelial carcinoma. Consequently, it is thought that Claudin-1 and Claudin-4 could help to differentiatelow-grade from high-grade and muscle-invasive from non-muscle-invasive urothelial carcinomas. In addition, it can be introduced as a possible therapeutic target.

Keywords: Claudin-1; Urothelial carcinoma; claudin-4; immunohistochemistry; urinary bladder.

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Carcinoma, Transitional Cell* / metabolism
  • Claudin-1
  • Claudin-4
  • Claudins
  • Humans
  • Male
  • Urinary Bladder / metabolism
  • Urinary Bladder Neoplasms* / pathology

Substances

  • Claudin-4
  • Claudin-1
  • Claudins
  • Biomarkers, Tumor