Expression of the caudal-type homeodomain transcription factor CDX2 is related to clinical outcome in biliary tract carcinoma.
OBJECTIVE
The caudal-type homeodomain transcriptional factor CDX2, a member of the caudal-related homeobox gene family, plays a crucial role in the regulation of cell proliferation and differentiation in the gut. Recent studies have reported that expression of CDX2 was an independent marker of outcome in patients with resected adenocarcinoma of ampulla of Vater, gastric cancer, and colon cancer. The clinicopathological significance of CDX2 expression has hitherto remained unclear in biliary tract carcinoma (BTC). The aim of this study was to determine whether CDX2 expression in BTC indicates clinical outcome.


METHODS
The expression of CDX2 was investigated immunohistochemically in surgically resected specimens from 164 patients with BTC, including 74 intrahepatic cholangiocarcinomas, 49 extrahepatic cholangiocarcinomas, and 41 gallbladder carcinomas. The correlation between expression of CDX2 and clinicopathological factors, including overall survival, tumor location, tumor stage, and degree of tumor differentiation, was examined in patients with BTC.


RESULTS
In total, 27 of the 164 (16.46%) patients with BTC expressed CDX2. The frequency of CDX2 expression was much higher in the extrahepatic cholangiocarcinomas (22.45%) and gallbladder carcinomas (29.27%) than in the intrahepatic cholangiocarcinomas (5.41%), the difference being statistically significant (P = 0.002). Factors influencing survival on univariate analysis were tumor stage (P < 0.00001), degree of tumor differentiation (P = 0.0002), and CDX2 expression (P = 0.01). On multivariate analysis using the Cox proportional hazard model, CDX2 expression and tumor stage were independent prognostic factors in patients with BTC.


CONCLUSIONS
Expression of CDX2 was an independent indicator of outcome in patients with BTC in addition to tumor stage and tumor differentiation. The mechanism by which CDX2 expression influences behavior of biliary tract carcinoma needs further investigation.
Chang
Yu-Ting
YT
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Hsu
Chiun
C
Jeng
Yung-Ming
YM
Chang
Ming-Chu
MC
Wei
Shu-Chen
SC
Wong
Jau-Min
JM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001661:Biliary Tract Neoplasms / Q000378:metabolism*; D000071616:CDX2 Transcription Factor; D002277:Carcinoma / Q000378:metabolism*; D005260:Female; D018398:Homeodomain Proteins / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015534:Trans-Activators / Q000096:biosynthesis*; D016896:Treatment Outcome
D000071616:CDX2 Transcription Factor; D018398:Homeodomain Proteins; D015534:Trans-Activators