3905 - Loss of CDX-2 expression is an independent poor prognostic biomarker in colorectal cancer

Background

Loss of caudal-type homeobox transcription factor-2 (CDX-2) expression in colorectal cancers (CRC) has recently been proposed as a predictive biomarker for response to chemotherapy and also prognosis. However, the data on relationship between alterations in CDX-2 expression and clinicopathological variables remain limited. We herein aimed to investigate the clinicopathological factors and prognostic implications associated with loss of CDX-2 expression in CRC patients.

Methods

Immunohistochemistry for CDX-2 expression was performed on formalin-fixed, paraffin-embedded tissue samples from 427 patients with CRC. Correlation between CDX-2 expression and clinicopathological characteristics were evaluated. Univariate and multivariate survival analyses were performed to reveal the prognostic value of loss of CDX-2 expression.

Results

Of 427 patients, 85% were stage I-III. Seventy six percent had left-sided primary tumors. Deficient mismatch repair (dMMR) was found in 12%. CDX-2-negative expression was identified in 18 out of 427 (4.2%) patients. Loss of CDX-2 expression was more commonly found in patient with right-sided tumors rather than left-sided tumors (9.4% vs 2.8% respectively, p = 0.005) and dMMR compared to proficient MMR (11.5% vs 3.3% respectively, p = 0.006). There was no association between CDX-2 expression and sex, stage, histologic subtype, tumor differentiation and lymphovascular/perineural invasion. By univariate analysis, patients with CDX-2 loss of expression had significantly worse overall survival (OS) and disease free survival (DFS) than those with CDX-2 positive expression (median OS 1.6 vs 11.6 months (mo), p < 0.001; median DFS 1.33 mo vs NR, p = 0.003). By multivariate analysis, loss of CDX-2 expression remained a negative prognostic factor for OS (hazard ratio 2.32; 95%CI 1.25-4.28, p = 0.007).

Conclusions

Loss of CDX-2 expression was associated with right-sided tumor and dMMR status. Moreover, loss of CDX-2 expression is a poor prognostic factor for OS, even among patients with dMMR tumors.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Faculty of Medicine Siriraj Hospital.

Disclosure

All authors have declared no conflicts of interest.