Assessment of CDX2 Expression as a Prognostic Marker in Colorectal Adenocarcinoma Patients from Uganda

Aim: The objective of this study was to determine the association between CDX2 and clinicopathological features of colorectal adenocarcinoma in Ugandan patients.

Introduction: Colorectal cancer (CRC) is one of the major cancer types worldwide. Although the burden of CRC is highest in developed countries, the Kampala Cancer Registry in Uganda, reports a steady rise in the incidence of early-onset CRC. Molecular markers such as CDX2 represent a bowel-specific tumour suppressor which inhibits the dissemination and progression of colorectal cancer. Recent advances in the field of cancer biology have introduced novel biomarkers such as CDX2 that hold promise in guiding personalized therapeutic decisions and have revolutionised prognostication. In developed high-income countries, the reduced expression of CDX2 identifies a sub-group of patients linked to a poor outcome.

Methodology: During the period 2008 to 2021, immunohistochemistry was carried out on 55 patients’ paraffin-embedded tissue blocks of CRC. CDX2 expression was detected using the indirect immunoperoxidase method which uses monoclonal antibody CDX2, DAKO Agilent USA, and Clone DAK-CDX2. The grade, LVI status and histopathological subtypes of CRC were evaluated using the haematoxylin and eosin stain. The demographic data, topography and stage of the tumours were obtained from the clinical patients’ files and the Kampala Cancer Registry.

Results: Out of 55 CRC participants that were studied, the mean age (SD) was 52.4 (15.8) years and the loss of CDX2 expression was 18.9% overall. Lack of CDX2 expression was significantly associated with lymphovascular invasion (LVI) (p=0.005). There were 55.6% that presented with poorly-differentiated adenocarcinoma compared to 22.2% presenting with well-differentiated adenocarcinoma in those that exhibited a lack of CDX2 expression, however, this was not statistically significant (p=0.126). In those exhibiting a lack of CDX2 expression, there were 40% of participants presented with stage IV disease compared to 20% of CRC participants with stage I disease (p=0.329). There was a negative correlation between the CRC grade and CDX2 expression (r=-0.0235) which did not reach statistical significance (p=0.8729). The findings in the present study in Ugandan patients, in keeping with previous studies in the West found that loss of CDX2 expression was associated with poor prognostic markers such as lymphovascular invasion. These findings from colorectal cancer patients in Uganda are testimony to the role of loss of CDX2 as a poor prognostic factor in colorectal adenocarcinoma.

Conclusions: Loss of CDX2 expression is associated with poor prognostic markers such as the presence of lymphovascular invasion in Ugandan patients. Loss of CDX2 expression is more frequently seen in advanced-stage colorectal cancer (CRC) because it is linked to a biologically aggressive tumor. More research in Uganda is required to determine how chemotherapy affects CDX2-negative tumors and how this relates to survival.