Utilization of CDX2 expression in diagnosing pancreatic ductal adenocarcinoma and predicting prognosis.
CDX2, a master transcriptional regulator of intestinal cell differentiation and survival, has been used as a marker to indicate colorectal lineage in adenocarcinomas of unknown origin. Pancreatic ductal adenocarcinoma (PDAC) is one of the most common causes for adenocarcinomas of unknown origin, but CDX2 expression in pancreatic disease remains unclear. In this study, we systemically and extensively investigated the expression and role of CDX2 in PDAC. We reported that CDX2 expression is weak and heterogeneous is all normal pancreas and chronic pancreatitis. It is largely expressed in epithelial-lining cells of pancreatic ducts including main ducts, inter-lobular ducts, intra-lobular ducts, intercalated ducts and centroacinar cells, but not in acinar cells or islet cells. CDX2 expression is down regulated during the transformation process from PanIN to PDAC. Only one third of PDACs retain some degree of CDX2 expression, and this group of PDACs have reduced median survival time compared to that of CDX2 negative group (308 days vs. 586 days, p = 0.0065). Metastatic PDACs remain similar expression pattern to that of the primary sites. Our study clearly demonstrates CDX2 expression in pancreatic diseases including PDAC, which is practically important when CDX2 is used to establish the primary sites of adenocarcinomas of unknown origin. In addition, our study also provides CDX2 as a prognostic marker for PDAC and implicates an important role of CDX2 in the development of normal pancreas and PDAC.
Department of Pathology, University Hospitals Case Medical Center, Cleveland, Ohio, United States of America ; Department of Pathology, Case Western Reserve University, Cleveland, Ohio, United States of America.
Wenbin
W
Xiao
Department of Pathology, University Hospitals Case Medical Center, Cleveland, Ohio, United States of America ; Department of Pathology, Case Western Reserve University, Cleveland, Ohio, United States of America.
Hong
H
Hong
Department of Pathology, University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
Amad
A
Awadallah
Department of Pathology, University Hospitals Case Medical Center, Cleveland, Ohio, United States of America ; Department of Pathology, Case Western Reserve University, Cleveland, Ohio, United States of America.
Lan
L
Zhou
Department of Pathology, University Hospitals Case Medical Center, Cleveland, Ohio, United States of America ; Department of Pathology, Case Western Reserve University, Cleveland, Ohio, United States of America.
Wei
W
Xin
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D000071616:CDX2 Transcription Factor; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010183:Pancreatic Ducts / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D050500:Pancreatitis, Chronic / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins