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

Ririn Endah Puspitasari; Upik Andriani Miskad; Muhammad Husni Cangara; Syarifuddin Wahid; Djumadi Achmad; Amalia Yamin; Suryani Tawali

doi:10.31557/apjcb.2026.11.1.41-48

Authors

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

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.