Prognostic Significance of Claudin-4 in Relation to Key Tumor Budding and Invasion Parameters in Colorectal Adenocarcinoma

Authors

  • Ririn Endah Puspitasari Department of Anatomical Pathology, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia. Author https://orcid.org/0009-0002-4231-6444 (unauthenticated)
  • Upik Andriani Miskad Department of Anatomical Pathology, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia. Department of Anatomical Pathology, Hasanuddin University Hospital, Makassar, Indonesia. Author https://orcid.org/0000-0002-1980-395X (unauthenticated)
  • Muhammad Husni Cangara Department of Anatomical Pathology, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia. Department of Anatomical Pathology, Hasanuddin University Hospital, Makassar, Indonesia. Author http://orcid.org/0000-0002-5160-8265 (unauthenticated)
  • Syarifuddin Wahid Department of Anatomical Pathology, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia. Department of Anatomical Pathology, Hasanuddin University Hospital, Makassar, Indonesia. Author
  • Djumadi Achmad Department of Anatomical Pathology, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia. Department of Anatomical Pathology, Hasanuddin University Hospital, Makassar, Indonesia. Author
  • Amalia Yamin Department of Anatomical Pathology, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia. Department of Anatomical Pathology, dr. Wahidin Sudirohusodo Hospital, Makassar, Indonesia. 4Department of Public Health, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia. Author https://orcid.org/0009-0008-5383-3408 (unauthenticated)
  • Suryani Tawali Department of Public Health, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia. Author http://orcid.org/0000-0002-2008-469X (unauthenticated)

DOI:

https://doi.org/10.31557/apjcb.2026.11.1.41-48

Keywords:

Claudin-4; Colorectal Adenocarcinoma; Tumor Budding; Deep Invasion; Prognostic Marker

Abstract

Objective: Colorectal cancer (CRC) is a major global health burden. Claudin-4, a tight junction protein preserving epithelial cohesion, has paradoxically been implicated in tumor progression. Its prognostic role in CRC remains unclear, particularly regarding histopathological grade, tumor budding, tumor-infiltrating lymphocytes (TILs), and deep invasion. This study aimed to clarify these associations.

Methods: This cross-sectional study included 95 formalin-fixed, paraffin-embedded colorectal adenocarcinoma specimens obtained from 2022 to 2024. Claudin-4 expression was assessed immunohistochemically using the TIS. Tumor budding was evaluated according to ITBCC 2016, TILs based on ITWG criteria, histopathological grade using the WHO classification, and deep invasion (pT1–pT3) based on the AJCC 8th edition. Statistical analysis was performed with Chi-square, Mann–Whitney, and Kruskal–Wallis tests.

Results: Strong Claudin-4 expression was found in 47.4% of cases. Expression correlated significantly with tumor budding (p = 0.038) and deep invasion (p = 0.038), but not with histopathological grade (p = 0.113) or TILs (p = 0.170). Mean TIS values showed a non-significant upward trend with grade and TIL density.

Conclusion: Claudin-4 is significantly associated with markers of invasiveness, supporting its value as a prognostic biomarker of tumor aggressiveness in colorectal adenocarcinoma.

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Published

2026-01-07

Issue

Vol. 11 No. 1 (2026)

Section

Research Articles/ Original Work

License

 West Asia Organization for Cabcer Prevention retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License 4 (This permits anyone to copy, distribute, transmit and adapt the published work, provided the original work and source are appropriately cited).