Expression of phosphorylated ERK1/2 and homeodomain protein CDX2 in cholangiocarcinoma.
OBJECTIVE
The extracellular signal-regulated kinase (ERK) 1/2 pathway plays important roles in the regulation of cell proliferation, differentiation and cell survival. The caudal-related homeobox protein CDX2 is essential for the development of the intestine, and is related to gastric and gallbladder cancers with the intestinal phenotype. However, the roles of ERK1/2 phosphorylation (pERK1/2) and CDX2 in cholangiocarcinogenesis remain unknown.


METHODS
We investigated the expression of pERK1/2, CDX2 and MUC2 in Thai cholangiocarcinoma (CCA) specimens by means of immunohistochemical staining, and compared the expression of these proteins with clinicopathological factors.


RESULTS
The pERK1/2 protein was expressed in 29 of 59 (49.2%) CCA cases. Interestingly, in tubular-type CCA, the frequency of pERK1/2 expression was associated with a higher grade of differentiation (P = 0.001). CDX2 expression was observed in 22 of the 59 (37.3%) CCA cases, showed a relationship with MUC2 expression (P = 0.001), and was much higher in papillary-type than tubular-type CCA (P = 0.002).


CONCLUSIONS
These results imply that pERK1/2 may be important for the differentiation of tubular-type CCA, while CDX2 is related to the intestinal phenotype of papillary-type CCA.
Jinawath
Artit
A
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
Yuasa
Yasuhito
Y
Pairojkul
Chawalit
C
D001650:Bile Duct Neoplasms / Q000378:metabolism* / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism* / Q000473:pathology; D000071616:CDX2 Transcription Factor; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000473:pathology; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D018398:Homeodomain Proteins / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000096:biosynthesis*; D048052:Mitogen-Activated Protein Kinase 3 / Q000096:biosynthesis*; D055262:Mucin-2; D009077:Mucins / Q000096:biosynthesis; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D004273:DNA, Neoplasm; D018398:Homeodomain Proteins; C117307:KRAS protein, human; C524625:MUC2 protein, human; D055262:Mucin-2; D009077:Mucins; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins