Impact of CDX2 expression status on the survival of patients after curative resection for colorectal cancer liver metastasis

Abstract

Background: The prognostic biomarker for patients undergoing curative liver metastasectomy for colorectal cancer (CRC) is lacking. The purpose was to investigate the prognostic role of a lack of CDX2 expression, which has been proposed as a potential biomarker for high-risk relapse in early-stage CRC, in patients undergoing curative liver metastasectomy. Methods: A total of 396 consecutive patients with CRC liver metastasis who underwent potentially curative liver metastasectomy at a single center in Japan between 2005 and 2015 were included. For the immunohistochemical analysis of nuclear CDX2 expression, we adopted the tissue microarray approach using the resected metastatic liver CRCs. Patient subgroups were compared with respect to disease-free survival (DFS) and overall survival (OS) by applying the Kaplan-Meier curve, log-rank tests, and multivariate analyses based on the Cox proportional hazards method. OS is defined as the period from the date of curative liver resection for metastatic CRC until death. DFS is defined as the length of time from curative liver resection to either the first recurrence or death. In patients without recurrence, the latest imaging inspection date was used as the censored date. Results: Thirty-six of the 396 CRCs (9.1%) reduced CDX2 expression. The reduced expression of CDX2 was associated with poor differentiation (P = 0.02). DFS in days was lower in the patients with CDX2-low CRC than in the patients with CDX2-high CRC (median DFS: 245 days versus 420 days; hazard ratio for disease recurrence: 1.64; 95% confidence interval: 1.08-2.38; P = 0.02). OS in days was lower in the patients with CDX2-low CRC than in the patients with CDX2-high CRC (median OS: 1024 days versus 3145 days; hazard ratio: 2.41; 95% confidence interval: 1.52-3.85; P < 0.001). In patients with CDX2-low CRC, both DFS and OS were similar between the with and without pre- or post-operative chemotherapy groups (median DFS: 243 versus 247 days; P = 0.73, median OS: 1016 versus 1363 days; P = 0.69). Conclusions: Reduced expression of CDX2 indicates poor DFS and OS, however, it might not represent chemosensitivity in patients undergoing curative liver metastasectomy. (339/350).