While the lack of CDX2 expression has recently been proposed as a potential biomarker for high relapse risk in patients with stage II and III colon cancer after complete surgical resection, its role in metastatic colorectal cancer (CRC) remains unclear. We conducted a retrospective analysis to characterize the clinicopathologic features of CDX2-negative metastatic CRC, and to assess the value of CDX2 loss as a potential prognostic and predictive biomarker for metastatic CRC.
We identified 66 patients with CDX2-negative metastatic CRC treated at our institution between 2006 and 2016, as well as a comparison cohort consisting of 79 patients with CDX2-positive metastatic CRC. Overall survival (OS) and progression-free survival (PFS) for first line systemic therapy were estimated using the Kaplan-Meier method. The associations of CDX2 expression with survival were evaluated using Cox proportional hazards regression models.
The prevalence of CDX2 loss in our cohort was 5.6%. Patients with CDX2-negative metastatic CRC were significantly more likely to be female (62% vs. 44%, p = 0.03), have right-sided primary tumors (55% vs. 34%, p = 0.01) of poorly-differentiated histology (55% vs. 24%, p = 0.0001), with distant lymph node metastasis (47% vs. 16%, p
CDX2 loss in metastatic CRC is an adverse prognostic feature and a negative predictor of response to chemotherapy. These promising results warrant validation in an independent cohort. In addition, future clinical trials should be considered to evaluate the optimal treatment strategy for this aggressive histology.
Clinical trial identification
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Minimal funding required from the Mayo Clinic Cancer Center
All authors have declared no conflicts of interest.