Expression of homeodomain protein CDX2 in gallbladder carcinomas.
OBJECTIVE
Caudal-related homeobox protein CDX2 plays an important role in the regulation of cell proliferation and differentiation of the intestinal epithelium. CDX2 is associated with intestinal metaplasia and carcinomas of the stomach, but the role of CDX2 in gallbladder carcinogenesis remains unknown.


METHODS
We analyzed the expression of CDX2 and intestinal apomucin MUC2 in gallbladder cancer cell lines at the mRNA level by the RT-PCR method. We also investigated the expression of CDX2 and MUC2 in 68 primary gallbladder carcinomas by the immunohistochemical staining method and compared the expression of CDX2 with the clinicopathological factors in the gallbladder carcinoma cases.


RESULTS
Expression of CDX2 and MUC2 was found in three of four gallbladder cancer cell lines at the mRNA level. In addition, we found that CDX2 was absent in the normal gallbladder epithelium, but the CDX2 protein was expressed in 25 of the 68 (36.8%) gallbladder carcinomas. Interestingly, in the tubular type gallbladder carcinomas, the frequency of CDX2 expression was much higher in the well-differentiated type than the moderately and poorly differentiated types, the difference being statistically significant (P<0.01). CDX2 expression showed a relationship with expression of MUC2 (P<0.04) in the gallbladder carcinomas. CDX2 was expressed in intestinal metaplasia and dysplasia, which are hypothesized to be premalignant conditions.


CONCLUSIONS
These results imply that CDX2 plays an important role in gallbladder carcinogenesis with intestinal differentiation.
Wu
Xiang-Song
XS
Department of Molecular Oncology, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Akiyama
Yoshimitsu
Y
Igari
Toru
T
Kawamura
Tohru
T
Hiranuma
Susumu
S
Shibata
Toshikatsu
T
Tsuruta
Kouji
K
Koike
Morio
M
Arii
Shigeki
S
Yuasa
Yasuhito
Y
D000368:Aged; D001483:Base Sequence; D000071616:CDX2 Transcription Factor; D017931:DNA Primers; D005260:Female; D005706:Gallbladder Neoplasms / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D055262:Mucin-2; D009077:Mucins / Q000235:genetics; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D017931:DNA Primers; D018398:Homeodomain Proteins; C524625:MUC2 protein, human; D055262:Mucin-2; D009077:Mucins; D012333:RNA, Messenger