Prognostic value of low CDX2 expression in colorectal cancers with a high stromal content - a short report

Lack of expression of the intestinal transcription factor CDX2 in colorectal cancer (CRC) identifies patients with a poor prognosis. This biomarker has previously been suggested to be prognostic in CRCs with a high stromal content based on mRNA expression data. We investigated the prognostic value of CDX2 expression in microsatellite stable CRC stratified by stromal content using microscopy-based techniques.

The study included a cohort of 236 patients with stage I-IV CRC. We assessed by microscopy the tumour-stroma ratio (TSR) and the immunohistochemical CDX2 intensity. We found that patients of the stroma-high group had a worse prognosis compared to those of the stroma-low group [disease-free survival in a multivariate analysis (DFS_multivariate) HR 1.52 (95% CI 1.05-2.21)]. In our cohort, low CDX2 expression (14.6%) showed prognostic value for DFS_multivariate [HR 1.93 (95% CI 1.16-3.23)]. Interestingly, when stratifying the cohort by TSR, no prognostic difference was observed related to CDX2 expression in stroma-low tumours. However, CDX2 expression was found to be prognostic within the stroma-high group [DFS_multivariate HR 3.02 (95% CI 1.49-6.13)]. The p value for interaction between TSR and CDX2 status was borderline significant in DFS (p = 0.071).

The present study confirms a poor outcome of patients with stroma-high tumours. Low CDX2 expression in tumours with a high stromal content identified patients with a particularly poor prognosis. The present study did not reveal a clear difference in TSR associated with CDX2 status and survival. This method, solely based on microscopy, identifies patients who have a high risk of relapse and a poor outcome, and who may benefit from targeted therapy.