Abstract
ObjectiveLoss of caudal-type homeobox transcription factor 2 (CDX2) expression in colorectal cancers (CRCs) has recently been proposed as a promising predictive biomarker for not only prognosis but also response to chemotherapy. However, the relationship between alterations in CDX2 expression during cancer progression and response to chemotherapy remains unclear. We herein aimed to determine the concordance of CDX2 expression between primary CRCs and corresponding liver metastases, in association with chemotherapy.ResultsPrimary CRCs exhibited heterogeneous CDX2 expression. Seven of the 144 CRCs in the cohort (4.9%, 95% confidential interval, 2.0%–9.8%) were CDX2-negative. The concordance rate of the CDX2 expression status in patients who did not receive chemotherapy was 100% (P = 0.041), whereas the concordance rate among patients who received chemotherapy only after primary resection was 96.3% (P = 0.005). Moreover, the concordance rate in patients who received chemotherapy before both primary resection and liver metastasectomy was 100% (P < 0.001).ConclusionCDX2 expression status was highly concordant between primary CRCs and corresponding liver metastases, independent of chemotherapy, suggesting that the CDX2 expression status in CRCs was not affected by metastasis or chemotherapy.MethodsA total of 144 consecutive patients with CRC who were treated at a single center in Japan between 2006 and 2014 were included. Formalin-fixed paraffin-embedded whole sections of surgically resected primary CRCs and corresponding liver metastases were assessed for CDX2 expression by immunohistochemistry.
Highlights
Caudal-type homeobox transcription factor 2 (CDX2) regulates gut epithelial development and maturation [1,2,3,4] and is expressed within nuclei of intestinal epithelial cells from proximal duodenum to distal rectum [5]
The concordance rate of the CDX2 expression status in patients who did not receive chemotherapy was 100% (P = 0.041), whereas the concordance rate among patients who received chemotherapy only after primary resection was 96.3% (P = 0.005)
CDX2 expression status was highly concordant between primary colorectal cancer (CRC) and corresponding liver metastases, independent of chemotherapy, suggesting that the CDX2 expression status in CRCs was not affected by metastasis or chemotherapy
Summary
Caudal-type homeobox transcription factor 2 (CDX2) regulates gut epithelial development and maturation [1,2,3,4] and is expressed within nuclei of intestinal epithelial cells from proximal duodenum to distal rectum [5]. Increased CDX2 expression, which is observed in approximately 90%–95% of colorectal adenocarcinomas [6, 7], is considered to be a highly sensitive and specific diagnostic marker for adenocarcinomas of intestinal origin [8,9,10]. Several retrospective studies suggested that the loss of CDX2 expression in colorectal cancers (CRCs) was associated with worse prognosis as well as several adverse prognostic variables, such as high histologic grade, BRAF mutations, and CpG island methylator phenotype positivity [16,17,18]. In metastatic CRCs, the loss of CDX2 expression was reported to be associated with lower chemotherapy efficacy [19]. It remains unclear whether the CDX2 expression status represents a chemosensitive phenotype
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