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

• Published in: World journal of gastroenterology : WJG Vol. 21; no. 5; pp. 1457 - 1467
• Main Author: Bae, Jeong Mo
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Inc 07.02.2015
• Subjects: Adult; Aged; Aged, 80 and over; Basic Study; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; CDX2 Transcription Factor; CDX2;CpG; Chi-Square Distribution; Colorectal Neoplasms - chemistry; Colorectal Neoplasms - genetics; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; Colorectal Neoplasms - therapy; Disease Progression; Disease-Free Survival; DNA Mutational Analysis; Down-Regulation; Female; Homeodomain Proteins - analysis; Humans; Immunohistochemistry; island; Kaplan-Meier Estimate; Male; methylator; Middle Aged; Multivariate Analysis; Mutation; Neoplasm Staging; phenotype;Microsatellit; Predictive Value of Tests; Proportional Hazards Models; Risk Factors; Time Factors; Treatment Outcome; Young Adult; CpG island methylator phenotype; Microsatellite instability; CDX2; Survival; Colorectal cancer
• ISSN: 1007-9327; 2219-2840; 2219-2840
• DOI: 10.3748/wjg.v21.i5.1457

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,Cp G 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,Cp G 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.