# Diagnostic Value of Biomarkers in the Diagnosis of Cholangiocarcinoma and Its Benign Mimickers

**Authors:** Elmira Zolfeghari Khiavy, Nasser Rakhshani, Hamid Rezvani, Behnaz Bouzari, Hossein Ajdarkosh, Mahshid Panahi, Hemin Ashayeri, Seyed Mir Yaghub Musaviani, Soheil Khalili, Ali Basi, Mohammad Hadi Karbalaie Niya

PMC · DOI: 10.30699/ijp.2025.2029980.3307 · Iranian Journal of Pathology · 2025-03-10

## TL;DR

This study evaluates the usefulness of four biomarkers in diagnosing cholangiocarcinoma and distinguishing it from benign conditions.

## Contribution

The study compares the diagnostic value of CD56, SMAD4, CEA, and p53 for cholangiocarcinoma and its benign mimickers.

## Key findings

- CEA and p53 showed significant associations with cholangiocarcinoma.
- SMAD4 loss and CD56 expression were not statistically significant in CCA diagnosis.

## Abstract

Cholangiocarcinoma (CCA) is a malignancy that accounts for approximately 3% gastrointestinal cancer. The aim of this study was to evaluate and compare the diagnostic value of CD56, SMAD4, CEA, and p53 biomarkers in diagnosing cholangiocarcinoma and its benign mimickers.

This retrospective cross-sectional study was conducted on 54 CCA specimens and 27 non-cancerous pancreatobiliary tissue samples diagnosed between 2018 and 2022. All specimens were evaluated using immunohistochemistry (IHC) staining for CD56, SMAD4, CEA, and p53 expression. The cut-off value of each marker was obtained from the respective kit instructions and previous studies. The results were analyzed using SPSS version 26. A significance level of less than 0.05 was considered statistically significant.

Of the 81 specimens, the mean age in the case and control groups was 57.33 ± 11.99 and 44.7 ± 16.69 years, respectively, and 51 (63%) samples were obtained from male patients. We found that 39.5% had grade III p53 expression, 13.5% had grade II p53 expression, 41.9% had grade III CEA expression, and 9.8% had grade II CEA expression. Additionally, 17.3% were positive for CD56 expression, and 7.4% showed SMAD4 loss. There were significant associations between the expression of CEA (79.6%) and p53 (74%) in the CCA group (p-value < 0.05). However, SMAD4 loss and CD56 expression were not statistically significant.

Expression of CEA and p53 based on IHC staining is associated with the occurrence of CCA. However, SMAD4 and CD56 were not significantly associated with CCA. Further survival analysis and sensitivity and specificity assessments are needed to obtain more comprehensive results.

## Linked entities

- **Genes:** NCAM1 (neural cell adhesion molecule 1) [NCBI Gene 4684], SMAD4 (SMAD family member 4) [NCBI Gene 4089], CEACAM5 (CEA cell adhesion molecule 5) [NCBI Gene 1048], TP53 (tumor protein p53) [NCBI Gene 7157]
- **Diseases:** cholangiocarcinoma (MONDO:0019087)

## Full-text entities

- **Genes:** NCAM1 (neural cell adhesion molecule 1) [NCBI Gene 4684] {aka CD56, MSK39, NCAM}, CEACAM3 (CEA cell adhesion molecule 3) [NCBI Gene 1084] {aka CD66D, CEA, CGM1, CGM1a, W264, W282}, SMAD4 (SMAD family member 4) [NCBI Gene 4089] {aka DPC4, JIP, MADH4, MYHRS}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}
- **Diseases:** gastrointestinal cancer (MESH:D005770), CCA (MESH:D018281), malignancy (MESH:D009369)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12142014/full.md

## References

38 references — full list in the complete paper: https://tomesphere.com/paper/PMC12142014/full.md

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Source: https://tomesphere.com/paper/PMC12142014