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CC BY 4.0 · Indian J Med Paediatr Oncol
DOI: 10.1055/s-0042-1750207
Original Article

Pattern of Expression of CDX2 in Colorectal Cancer and its Role in Prognosis: An Ambispective Observational Study

Jagdeep Singh
1   Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India
2   Department of Medical Oncology, Dayanand Medical College, Ludhiana, Punjab, India
,
N G. Rajesh
3   Department of Pathology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India
,
Biswajit Dubashi
1   Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India
,
Nanda K. Maroju
4   Department of General Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India
,
Prasanth Ganesan
1   Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India
,
Kiran K. Matta
1   Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India
,
I Charles
1   Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India
,
Smita Kayal 
1   Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India
› Author Affiliations Funding Fund for this study was provided from intramural grant by Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, India, vide Letter no. JIP/Res/Intra-DM-Mch/phs1/01/2016–17 dated 09.09.2016 of INR 150,000.
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Abstract

Introduction Caudal-type homeobox 2 (CDX2), a nuclear protein, is essential for the proliferation and development of intestinal epithelial cells and is frequently downregulated during tumorigenesis. CDX2 inhibits cell growth as well as stimulates differentiation by activating intestinal specific genes, thus lack of CDX2 favors tumor growth and aggressiveness.

Objectives We aimed to evaluate the pattern of CDX2 expression in all stages of colorectal cancer (CRC) and study its association with baseline characteristics and prognosis.

Materials and Methods Study was conducted as an ambispective observational study, enrolling cases of CRC retrospectively from January 2014 to July 2016 (30 months), and prospectively during next 18-month period till January 2018. We performed CDX2 staining by immunohistochemistry on the available biopsy blocks of CRC patients during the study period. Total 286 patients were registered during the study period, of which only 110 biopsy blocks were available for staining. CDX2 scoring was done by a semiquantitative method on whole tissue section for the intensity and percentage of the cells showing positivity. Correlation of CDX2 expression was done with baseline clinical and histopathologic characteristics, and survival.

Results Of 110 patients, 77 (70%) constituted colon cancer and 33 (30%) were rectal cancer. The median age was 54.2 years, 62 (56.4%) being male and 48 (43.6%) female with male-to-female ratio 1.3:1. In the study cohort, 33 (30%) patients had stage II disease, 30 (27.3%) stage III, and 47 (42.7%) were stage IV. Seventy-three (66.4%) were positive for CDX2 and 37 (33.4%) were negative. Loss of CDX2 expression was significantly associated with advanced stage, rectal site, poor grade of differentiation, and presence of lymphovascular invasion (LVSI). With median follow-up of 16 months, progression-free survival (PFS) at 2 years was 30% for CDX2 negative patients compared with 67% for CDX2 positive (p = 0.009), while overall survival (OS) at 2 years was 46% for CDX2 negative versus 77% for positive patients (p = 0.01).

Conclusion Loss of CDX2 expression is associated with advanced stage, higher tumor grade, presence of LVSI, and worse PFS and OS and thereby functions as a poor prognostic factor in CRC.

Keywords

colorectal cancer - CDX2 - pattern - survival - prognosis

Authors' Contributions

Study concept and design: S.K., J.S., B.D., N.G.R. Provision of patient and study material: J.S., N.G.R., B.D., S.K., P.G., N.K.M., I.C. Performance and interpretation of IHC (immunohistochemistry): J.S., N.G.R., I.C. Data collection and analysis: J.S., N.G.R., S.K., B.D., K.K.M., I.C. Manuscript writing: J.S., S.K., B.D., P.G., N.G.R., N.K.M. Final approval of manuscript: all authors.


Declaration

Manuscript has been read and approved by all the authors, the requirements for authorship as stated earlier in this document have been met, and all author believes that the manuscript represents honest work.


Justification for authors more than 6: this study was an interdepartmental work, initiated by department of medical oncology in collaboration with departments of pathology and surgery. Authorship has been attributed to all the researchers who have made substantial contributions to the work as per the ICMJE authorship criteria.




Publication History

Article published online:
28 November 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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