Skip to main content
Log in

CDX2 Protein Expression in Colorectal Cancer and ItsCorrelation with Clinical and Pathological Characteristics, Prognosis, and Survival Rate of Patients

  • Original Research
  • Published:
Journal of Gastrointestinal Cancer Aims and scope Submit manuscript

Abstract

Purpose

Caudal-type homeobox transcription factor 2 (CDX2) is expressed in the nucleus of the intestinal epithelial cells and is essential for embryonic formation and differentiation of the intestine, whose reduced expression can result in metastatic tumors. This study was to investigate the association of CDX2 expression level in colorectal cancer (CRC) with age, gender, microscopic histopathology, tumor staging, tumor grading, 3-year survival rate, and prognosis.

Methods

After preparing paraffin tissue blocks, CDX2 protein expression was assayed by immunohistochemistry in 82 CRC patients. Hematoxylin and eosin staining was used to detect tumor histology, tumor grading, tumor staging, and blood-lymphatic, and neural invasion. The collected data includes age, gender, tumor site, and 3-year survival rate of patients after diagnosis.

Results

The CDX2 expression was significantly higher in men than in women, and it was significantly lower in right-sided tumors as in transverse colon and left-sided tumors. Also, the CDX2 expression was significantly higher in adenocarcinoma than in mucinous. In addition, a significant correlation was found between downregulated CDX2 and lymph node involvement. In tumor grading, there was a significant correlation between CDX2 downregulation and high-grade tumor. Moreover, there was a significant correlation between downregulated CDX2 expression and overall pathological staging.

Conclusion

The downregulated CDX2 expression is associated with female gender, right-sided tumors, mucinous tumors, lymph node involvement, high-grade tumor, and advanced overall pathological staging and can be considered as a possible prognostic factor for patients follow-up. However, our study is a preliminary study and further studies with larger sample sizes in different ethnic groups are required.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.

    Article  Google Scholar 

  2. Mousavi SM, Gouya MM, Ramazani R, Davanlou M, Hajsadeghi N, Seddighi Z. Cancer incidence and mortality in Iran. Ann Oncol. 2008;20(3):556–63.

    Article  Google Scholar 

  3. Jeon J, Du M, Schoen RE, Hoffmeister M, Newcomb PA, Berndt SI, et al. Determining risk of colorectal cancer and starting age of screening based on lifestyle, environmental, and genetic factors. Gastroenterology. 2018;154(8):2152–64 e19.

    Article  Google Scholar 

  4. Hamilton S R, Aaltonen L A, editors., eds. Carcinoma of the colon and rectum. World health organization classification of tumors Pathology and genetics of tumors of the Digestive System Lyon, Frances: IARC Pres; 2000:105–19.

  5. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100(1):57–70.

  6. Gervasoni A, Munoz RMM, Wengler GS, Rizzi A, Zaniboni A, Parolini O. Molecular signature detection of circulating tumor cells using a panel of selected genes. Cancer Lett. 2008;263(2):267–79.

    Article  CAS  Google Scholar 

  7. De Lott LB, Morrison C, Suster S, Cohn DE, Frankel WL. CDX2 is a useful marker of intestinal-type differentiation: a tissue microarray–based study of 629 tumors from various sites. Arch Pathol Lab Med. 2005;129(9):1100–5.

    PubMed  Google Scholar 

  8. Simmini S, Bialecka M, Huch M, Kester L, Van De Wetering M, Sato T, et al. Transformation of intestinal stem cells into gastric stem cells on loss of transcription factor Cdx2. Nat Commun. 2014;5:5728.

    Article  CAS  Google Scholar 

  9. Olsen AK, Coskun M, Bzorek M, Kristensen MH, Danielsen ET, Jørgensen S, et al. Regulation of APC and AXIN2 expression by intestinal tumor suppressor CDX2 in colon cancer cells. Carcinogenesis. 2013;34(6):1361–9.

    Article  CAS  Google Scholar 

  10. Kaimaktchiev V, Terracciano L, Tornillo L, Spichtin H, Stoios D, Bundi M, et al. The homeobox intestinal differentiation factor CDX2 is selectively expressed in gastrointestinal adenocarcinomas. Mod Pathol. 2004;17(11):1392.

    Article  CAS  Google Scholar 

  11. Barbareschi M, Murer B, Colby T, Chilosi M, Macri E, Loda M, et al. CDX-2 homeobox gene expression is a reliable marker of colorectal adenocarcinoma metastases to the lungs. Am J Surg Pathol. 2003;27(2):141–9.

    Article  CAS  Google Scholar 

  12. Moskaluk CA, Zhang H, Powell SM, Cerilli LA, Hampton GM, Frierson HF Jr. Cdx2 protein expression in normal and malignant human tissues: an immunohistochemical survey using tissue microarrays. Mod Pathol. 2003;16(9):913.

    Article  Google Scholar 

  13. Brabletz T, Spaderna S, Kolb J, Hlubek F, Faller G, Bruns CJ, et al. Down-regulation of the homeodomain factor Cdx2 in colorectal cancer by collagen type I: an active role for the tumor environment in malignant tumor progression. Cancer Res. 2004;64(19):6973–7.

    Article  CAS  Google Scholar 

  14. Kim JH, Rhee Y-Y, Bae JM, Cho N-Y, Kang GH. Loss of CDX2/CK20 expression is associated with poorly differentiated carcinoma, the CpG island methylator phenotype, and adverse prognosis in microsatellite-unstable colorectal cancer. Am J Surg Pathol. 2013;37(10):1532–41.

    Article  Google Scholar 

  15. Bae JM, Lee TH, Cho N-Y, Kim T-Y, Kang GH. Loss of CDX2 expression is associated with poor prognosis in colorectal cancer patients. World J Gastroenterol: WJG. 2015;21(5):1457.

    Article  CAS  Google Scholar 

  16. Baba Y, Nosho K, Shima K, Freed E, Irahara N, Philips J, et al. Relationship of CDX2 loss with molecular features and prognosis in colorectal cancer. Clin Cancer Res. 2009;15(14):4665–73.

    Article  CAS  Google Scholar 

  17. Group DCC. Danish Colorectal Cancer Group. Retningslinier for diagnostik og behandling af kolorektal cancer. 2009 (Accessed October 29, 2012)http://www.dccg.dk/03_Publikation/Retningslinier2009revOKT2010.pdf

  18. Bonhomme C, Duluc I, Martin E, Chawengsaksophak K, Chenard M, Kedinger M, et al. The Cdx2 homeobox gene has a tumour suppressor function in the distal colon in addition to a homeotic role during gut development. Gut. 2003;52(10):1465–71.

    Article  CAS  Google Scholar 

  19. Sobin L, Wittekind Ch (Eds.). TNM Classification of Malignant Tumours (Sixth Edition), Wiley-Liss, New York 2002:99-103

  20. Wang Y, Li Z, Li W, Liu S, Han B. Methylation of promoter region of CDX2 gene in colorectal cancer. Oncol Lett. 2016;12(5):3229–33.

    Article  CAS  Google Scholar 

  21. 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. 2003;27(3):303–10.

    Article  Google Scholar 

  22. Winn B, Tavares R, Matoso A, Noble L, Fanion J, Waldman SA, et al. Expression of the intestinal biomarkers Guanylyl cyclase C and CDX2 in poorly differentiated colorectal carcinomas. Hum Pathol. 2010;41(1):123–8.

    Article  CAS  Google Scholar 

  23. Dawson H, Koelzer VH, Lukesh A, Mallaev M, Inderbitzin D, Lugli A, et al. Loss of Cdx2 expression in primary tumors and lymph node metastases is specific for mismatch repair-deficiency in colorectal cancer. Front Oncol. 2013;3:265.

    Article  Google Scholar 

  24. Platet N, Hinkel I, Richert L, Murdamoothoo D, Moufok-Sadoun A, Vanier M, et al. The tumor suppressor CDX2 opposes pro-metastatic biomechanical modifications of colon cancer cells through organization of the actin cytoskeleton. Cancer Lett. 2017;386:57–64.

    Article  CAS  Google Scholar 

  25. 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. 2016;374(3):211–22.

    Article  CAS  Google Scholar 

  26. Lugli A, Tzankov A, Zlobec I, Terracciano LM. Differential diagnostic and functional role of the multi-marker phenotype CDX2/CK20/CK7 in colorectal cancer stratified by mismatch repair status. Mod Pathol. 2008;21(11):1403.

    Article  CAS  Google Scholar 

  27. Bafrani HH, Ahmadi M, Jahantigh D, Karimian M. Association analysis of the common varieties of IL17A and IL17F genes with the risk of knee osteoarthritis. J Cell Biochem. 2019;120(10):18020–30.

    Article  CAS  Google Scholar 

  28. Karimian M, Aftabi Y, Mazoochi T, Babaei F, Khamechian T, Boojari H, et al. Survivin polymorphisms and susceptibility to prostate cancer: a genetic association study and an in silico analysis. EXCLI J. 2018;17:479–91.

Download references

Acknowledgments

The authors sincerely express their appreciation to the Vice Chancellor for Research and Technology, Kashan University of Medical Sciences, Kashan, Iran.

Availability of Data and Materials

The dataset used in the current project is available with the authors and can be made available upon request.

Funding

The financial support for the current research was provided by Research Deputy of Kashan University of Medical Sciences, Kashan, Iran (grant numbers: 96144).

Author information

Authors and Affiliations

Authors

Contributions

TK and TM participated in the design of study. SAK and MK collected and documented the data and analyzed them. MK and SAK wrote the initial draft. All of the authors participated in draft revision and paper finalization.

Corresponding author

Correspondence to Tahereh Khamehchian.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflicts of interest.

Ethical Approval

The informed consent form was obtained from the study subjects. This study was approved by the Ethics Committee of Kashan University of Medical Sciences (Code of Ethics: IR.KAUMS.MEDNT.REC.1396.75).

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Asgari-Karchekani, S., Karimian, M., Mazoochi, T. et al. CDX2 Protein Expression in Colorectal Cancer and ItsCorrelation with Clinical and Pathological Characteristics, Prognosis, and Survival Rate of Patients. J Gastrointest Canc 51, 844–849 (2020). https://doi.org/10.1007/s12029-019-00314-w

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12029-019-00314-w

Keywords

Navigation