Iranian Journal of Pathology

Evaluation of the Role of Claudin-4 Antigen Overexpression in Triple-Negative Breast Cancer Patients: A 5-Year Survival Analysis

Document Type : Original Research

Authors

Maryam Soltan 1
Azar Naimi 1
Razieh Hafez forghan 2
Marjan Mansourian 3

1 Department of Pathology, Reproductive Sciences and Sexual Health Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

2 School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

3 School of Health, Department of Biostatistics and Epidemiology, Isfahan University of Medical Sciences, Isfahan, Iran

https://doi.org/10.30699/ijp.2025.2040168.3350
Abstract
Background & Objective: Breast cancer (BC) can be categorized into 4 groups based on molecular and pathological evidence: Luminal A, Luminal B, HER2+ tumors, and triple-negative breast cancer (TNBC). TNBC has a poorer survival rate and a higher chance of recurrence and metastasis compared to other BC types, primarily due to its challenging treatment course. Claudin 4 (CLDN4), a transmembrane protein in tight junctions between cells, has been linked to poor prognosis and faster disease progression in these malignancies.
Methods: Patients previously diagnosed with TNBC and tested for CLDN4 overexpression were contacted for follow-up and to determine disease outcomes. The current health status, cause, and time of death (if applicable) were recorded. Patient files were accessed to obtain information on age, tumor size and grading, lymph node involvement, metastasis, Ki67, and CLDN4 expression.
Results: Patients with high CLDN expression showed a significantly lower mortality rate. However, after controlling for other covariates, the hazard ratio (HR) was 0.48 (95%CI= [0.13 – 1.27]) in the crude model for survival, 0.54 (95%CI = [0.2 – 1.43]) when adjusted for age at diagnosis, and 0.58 (95%CI = [0.18-1.82]) when adjusted for other covariates. CLDN4 was also not correlated with tumor metastasis (HR=0.64, p=0.203, in the crude model; HR=0.52, p=0.409, when adjusted for other covariates). Patients in the CLDN4 high group had a significantly higher number of tumors >2cm.
Conclusion: Although previous studies have shown that CLDN4 overexpression worsens TNBC prognosis and increases metastasis or recurrence, the current study found no such association.

Keywords

Breast Neoplasms
Claudin-4
Biomarkers
Prognosis
Neoplasm Metastasis

Subjects

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Iranian Journal of Pathology
Volume 20, Issue 2
Spring 2025
Pages 167-172

  • Receive Date 02 September 2024
  • Revise Date 14 December 2024
  • Accept Date 05 February 2025

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