The role of CDX2 immunohistochemical marker in colorectal adenocarcinoma « CDX2 in colorectal adenocarcinoma »

##plugins.themes.academic_pro.article.sidebar##

Published Dec 27, 2025
https://doi.org/10.62438/tunismed.v103i10.6093
Download
Vol. 103 No. 10 (2025): Tunis Med Oct 2025

##plugins.themes.academic_pro.article.main##

Sarra Ben Rejeb
Pathology department, Security Forces Hospital, LaMarsa , Research Unity UR17ES17 on Epithelial to Mesenchymal Transition, Faculty of medicine of Tunis, Tunisia
Dhouha Bacha
Pathology department, Monji Slim Hospital, Marsa Tunisia
Haifa Rachdi
Oncoloy department, Abderrahmen Mami Hospital, Ariana, Tunisia
Khadija Bellil
Research Unity UR17ES17 on Epithelial to Mesenchymal Transition, Faculty of medicine of Tunis, Tunisia

Abstract

Introduction: Caudal-type homeobox transcription factor 2 (CDX2), a marker of intestinal differentiation, has shown potential as a prognostic biomarker in colorectal cancer(CRC). Its loss is associated with aggressive disease features and poor survival, yet its routine clinical use remains limited. In this study, we aimed to explore the immunohistochemical expression of CDX2 in sporadic colorectal adenocarcinomas and to assess its prognostic significance.


Methods: This was a retrospective longitudinal study including patients with sporadic colorectal adenocarcinoma. CDX2 expression was assessed via automated immunohistochemistry on formalin-fixed, paraffin-embedded sections using monoclonal antibody CDX2-DAK (Dako, Glostrup, Denmark). Only nuclear staining was considered positive. Clinicopathological data, including tumor stage, differentiation, and survival, were collected over a 36-month median follow-up. Statistical analysis was performed using SPSS version 20 (p < 0.05).


Results: Thirty cases were included with a mean age of 57 ± 2 years and a male-to-female ratio of 1.7. CDX2 expression was observed in 80% (24/30) of tumors. Its loss was significantly associated with poor differentiation (p=0.04),lymph node involvement (p=0.0027), advanced stage (p=0.043), and reduced overall survival (p=0.0024). Loss of CDX2 expression combined with pT4 stage identified a high-risk subgroup with worse disease-free and overall survival. Tumors were predominantly colonic (80%), with 90% adenocarcinomas and 10% mucinous carcinomas.


Conclusions: CDX2 loss is a robust prognostic indicator in CRC, particularly when combined with pT4 stage, highlighting its potential for risk stratification and treatment planning. Larger, prospective studies are needed to standardize CDX2 assessment and validate its clinical utility in colorectal adenocarcinoma.

Keywords:

CDX2, colorectal, adenocarcinoma, immunohistochemistry, prognostic marker

##plugins.themes.academic_pro.article.details##

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

References

  1. Chan WY, Chua W, Wilkinson K, Epitakaduwa C, Mandaliya H, Descallar J, et al. The Prognostic and Predictive Utility of CDX2 in Colorectal Cancer. Int J Mol Sci. 8 août 2024;25(16):8673.
  2. Werling RW, Yaziji H, Bacchi CE, Gown AM. CDX2, a Highly Sensitive and Specific Marker of Adenocarcinomas of Intestinal Origin: An Immunohistochemical Survey of 476 Primary and Metastatic Carcinomas. Am J Surg Pathol. mars 2003;27(3):303‑10.
  3. Al-Duhaidahawi M. Role of CDX2 Marker in Patients with Colorectal Cancer. Biomed Chem Sci. 1 janv 2023;2(1):11‑5.
  4. Aasebø K, Dragomir A, Sundström M, Mezheyeuski A, Edqvist PH, Eide GE, et al. CDX2: A Prognostic Marker in Metastatic Colorectal Cancer Defining a Better BRAF Mutated and a Worse KRAS Mutated Subgroup. Front Oncol. 11 févr 2020;10:8.
  5. Çalik İ, Çalik M, Özercan İH, Dağli AF, Artaş G, Türken G, et al. Decreased CDX2 Expression Adversely Effect On Prognosis Of Patients With Colorectal Cancer. Dicle Tıp Derg. 18 mars 2020;57‑65.
  6. Choi HB, Pyo JS, Son S, Kim K, Kang G. Diagnostic and Prognostic Roles of CDX2 Immunohistochemical Expression in Colorectal Cancers. Diagnostics. 20 mars 2022;12(3):757.
  7. Tomasello G, Barni S, Turati L, Ghidini M, Pezzica E, Passalacqua R, et al. Association of CDX2 Expression With Survival in Early Colorectal Cancer: A Systematic Review and Meta-analysis. Clin Colorectal Cancer. juin 2018;17(2):97‑103.
  8. Badia-Ramentol J, Gimeno-Valiente F, Duréndez E, Martínez-Ciarpaglini C, Linares J, Iglesias M, et al. The prognostic potential of CDX2 in colorectal cancer: Harmonizing biology and clinical practice. Cancer Treat Rev. déc 2023;121:102643.
  9. Den Uil SH, De Wit M, Slebos RJC, Delis-van Diemen PM, Sanders J, Piersma SR, et al. Quantitative analysis of CDX2 protein expression improves its clinical utility as a prognostic biomarker in stage II and III colon cancer. Eur J Cancer. févr 2021;144:91‑100.
  10. Mukohyama J, Agawa K, Yamashita K, Matsuda T, Shinoda M, Itano O, et al. CDX2 Is a Prognostic Biomarker for Unresectable Metastatic Colorectal Cancer. Anticancer Res. août 2023;43(8):3763‑7.
  11. Konukiewitz B, Schmitt M, Silva M, Pohl J, Lang C, Steiger K, et al. Loss of CDX2 in colorectal cancer is associated with histopathologic subtypes and microsatellite instability but is prognostically inferior to hematoxylin–eosin-based morphologic parameters from the WHO classification. Br J Cancer. 7 déc 2021;125(12):1632‑46.
  12. Rachdi Bayar H. Intérêt pronostique du CDX2 dans les cancers colorectaux à propos de 30 cas. [Tunis]: Faculté de médecine de Tunis; 2017.
  13. Singh J. Pattern of expression of CDX2 in colorectal cancer and its role in prognosis. J Clin Oncol. 20 mai 2019;37(15_suppl):e15115‑e15115.
  14. Xu W, Zhu Y, Shen W, Ding W, Wu T, Guo Y, et al. Combination of CDX2 expression and T stage improves prognostic prediction of colorectal cancer. J Int Med Res. mai 2019;47(5):1829‑42.
  15. Nishiuchi A, Hisamori S, Sakaguchi M, Fukuyama K, Hoshino N, Itatani Y, et al. MicroRNA-9-5p-CDX2 Axis: A Useful Prognostic Biomarker for Patients with Stage II/III Colorectal Cancer. Cancers. 27 nov 2019;11(12):1891.
  16. Korphaisarn K, Pongpaibul A, Sukhokanjanachusak K, Akewanlop C. Loss of CDX-2 expression is an independent poor prognostic biomarker in colorectal cancer. Ann Oncol. oct 2019;30:v210.
  17. Caldas ÁMC, Nunes WA, Taboada R, Cesca MG, Germano JN, Riechelmann RP. oss of CDX2 and high COX2 (PTGS2) expression in metastatic colorectal cancer. ecancermedicalscience [Internet]. 8 févr 2024 [cité 14 mai 2025];18. Disponible sur: https://ecancer.org/en/journal/article/1666-loss-of-cdx2-and-high-cox2-ptgs2-expression-in-metastatic-colorectal-cancer
  18. Wang Y shuai, Kou Y, Zhu R tao, Han B wei, Li C hui, Wang H jian, et al. CDX2 as a Predictive Biomarker Involved in Immunotherapy Response Suppresses Metastasis through EMT in Colorectal Cancer. Zhong WL, éditeur. Dis Markers. 12 oct 2022;2022:1‑13.
  19. Yang J, Antin P, Berx G, Blanpain C, Brabletz T, Bronner M, et al. Guidelines and definitions for research on epithelial–mesenchymal transition. Nat Rev Mol Cell Biol. 10 juin 2020;21(6):341‑52.
  20. Dalerba P, Sahoo D, Paik S, Guo X, Yothers G, Song N, et al. CDX2 as a Prognostic Biomarker in Stage II and Stage III Colon Cancer. N Engl J Med. 21 janv 2016;374(3):211‑22.