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. 2015 Feb 7;21(5):1457-67.
doi: 10.3748/wjg.v21.i5.1457.

Loss of CDX2 expression is associated with poor prognosis in colorectal cancer patients

Jeong Mo Bae  1 , Tae Hun Lee  1 , Nam-Yun Cho  1 , Tae-You Kim  1 , Gyeong Hoon Kang  1
Affiliations

Loss of CDX2 expression is associated with poor prognosis in colorectal cancer patients

Jeong Mo Bae et al. World J Gastroenterol. .

Abstract

Aim: To investigate the clinicopathologic characteristics and prognostic implications associated with loss of CDX2 expression in colorectal cancers (CRCs).

Methods: We immunohistochemically evaluated CDX2 expression in 713 CRCs and paired our findings to clinicopathologic and molecular characteristics of each individual. Endpoints included cytokeratin 7 and CK20 expression, microsatellite instability, CpG island methylator phenotype, and KRAS and BRAF mutation statuses. Univariate and multivariate survival analysis was performed to reveal the prognostic value of CDX2 downregulation.

Results: CDX2 expression was lost in 42 (5.9%) patients. Moreover, loss of CDX2 expression was associated with proximal location, infiltrative growth, advanced T, N, M and overall stage. On microscopic examination, loss of CDX2 expression was associated with poor differentiation, increased number of tumor-infiltrating lymphocytes, luminal serration and mucin production. Loss of CDX2 expression was also associated with increased CK7 expression, decreased CK20 expression, CpG island methylator phenotype, microsatellite instability and BRAF mutation. In a univariate survival analysis, patients with loss of CDX2 expression showed worse overall survival (P < 0.001) and progression-free survival (P < 0.001). In a multivariate survival analysis, loss of CDX2 expression was an independent poor prognostic factor of overall survival [hazard ratio (HR) = 1.72, 95%CI: 1.04-2.85, P = 0.034] and progression-free survival (HR = 1.94, 95%CI: 1.22-3.07, P = 0.005).

Conclusion: Loss of CDX2 expression is associated with aggressive clinical behavior and can be used as a prognostic marker in CRCs.

Keywords: CDX2; Colorectal cancer; CpG island methylator phenotype; Microsatellite instability; Survival.

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Figures

Figure 1
Figure 1
Immunohistochemical study findings of colorectal cancers (magnification × 200). A: CK7 expression; B: Retained CK20 expression; C: Retained CDX2 expression; D: CK7 no-expression; E: Decreased CK20 expression; F: Loss of CDX2 expression. CK: Cytokeratin.
Figure 2
Figure 2
Histogram for loss of CDX2 expression using two different anti-CDX2 primary antibodies in immunohistochemistry. A, B: Histogram of CDX2 expression according to CIMP status (A: CDX2-88; B: EPR2764Y); C, D: Histogram of CDX2 expression according to MSI status (C: CDX2-88; D: EPR2764Y). CIMP: CpG island methylator phenotype; MSI: Microsatellite instability; MSS: Microsatellite stable.
Figure 3
Figure 3
Kaplan-Meier survival curves according to CDX2 expression in colorectal cancers. A: Overall survival (P < 0.001); B: Progression-free survival (P < 0.001). Linear line: Retained CDX2 expression, dashed line: Loss of CDX2 expression. Cut-off for loss of CDX2 expression < 20% of tumor cells showing nuclear positivity.
See this image and copyright information in PMC

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