Loss of CDX2/CK20 Expression Is Associated With Poorly Differentiated Carcinoma, the CpG Island Methylator Phenotype, and Adverse Prognosis in Microsatellite-unstable Colorectal Cancer

Abstract

Several previous studies have demonstrated that the CDX2-negative (CDX2) and/or CK20-negative (CK20) phenotypes of colorectal cancers (CRCs) might be associated with high levels of microsatellite instability (MSI-H). The aim of this study was to investigate the clinicopathologic and molecular features of MSI-H CRCs with different CDX2/CK20 expression statuses. The CDX2 and CK20 expression statuses were immunohistochemically evaluated in 109 MSI-H CRC tissue samples, and the correlations of these statuses with clinicopathologic, molecular, and survival data were statistically analyzed. Of the 109 MSI-H CRCs, 15 were CDX2 (13.8%), and 19 were CK20 (17.4%). The simultaneous loss of CDX2 and CK20 expression (CDX2/CK20) was observed in 9 cases (8.3%). CDX2 loss was correlated with lymph node metastasis, poor differentiation, MLH1 loss, the mutation of BRAF, and CpG island methylator phenotype-high (CIMP-H) status. Right-sided tumor location, nodal metastasis, poor differentiation, and CIMP-H status were significant characteristics of CK20 tumors. The CDX2/CK20 phenotype was associated with older age (above 56 y), higher stage (stage III or IV), deep invasion (pT3 or pT4), lymph node metastasis (pN1 or pN2), poor differentiation (nonmedullary/non-signet ring cell type), the mutation of BRAF, and CIMP-H status among MSI-H CRCs. Patients with CDX2/CK20 tumors exhibited worse overall and disease-free survival compared with the patients with CDX2 and/or CK20 tumors (P<0.001). In the multivariate analysis for disease-free survival, the CDX2/CK20 phenotype was an independent prognostic factor for MSI-H CRC (P=0.030, hazard ratio=3.288). The CDX2/CK20 phenotype defines a distinct subgroup of MSI-H CRCs with poor differentiation, CIMP-H status, and unfavorable prognosis.

Predictive value of CK20 in evaluating the efficacy of treatment and prognosis after surgery for colorectal cancer

“…Recently, the CK20 protein has received increased interest due to its highly specific expression in both colorectal and gastric cancers (Kim et al, 2009;Sun et al, 2012;Kim et al, 2013;Tunca et al, 2013). In these cells, CK20 protein is highly expressed, with features including irregular modulation, loss of polarity, and diffuse distribution (Šamija et al, 2012).…”

Bladder cancer in a young patient: Undiscovered risk factors

“…However, such correlations in a non-smoker at a young age cannot be proven and thus this case illustrates a rare incidence of mucinous adenocarcinoma with no known risk factor. CK20 and CDX2 were tumor markers found to be expressed in the tumor from the present patient and have previously been shown to be prominent in some other malignancies, such as colorectal cancer (7). It therefore raises the hypothesis, whether a family history of colon cancer increases the risk of bladder cancer at a younger age and whether a patient with a positive family history of colon cancer with particular markers should have early screening for bladder cancer.…”

Comment on ‘Cytokeratin 20-negative Merkel cell carcinoma is infrequently associated with the Merkel cell polyomavirus‘

“…5 In our previous study, 6 we demonstrated that MCPyV-negative MCCs show more poorly differentiated features, such as severe nuclear atypia and pleomorphism, than MCPyV-positive MCCs. The combination of CK20 expression loss and MCPyV negativity may be associated with the poorly differentiated MCC features.…”