Expression of phosphorylated ERK1/2 and homeodomain protein CDX2 in cholangiocarcinoma

• Published in: Journal of cancer research and clinical oncology 2006-12, Vol.132 (12), p.805-810
• Main Authors: JINAWATH, Artit, AKIYAMA, Yoshimitsu, YUASA, Yasuhito, PAIROJKUL, Chawalit
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Bile Duct Neoplasms - metabolism; Bile Duct Neoplasms - pathology; Bile Ducts, Intrahepatic - metabolism; Bile Ducts, Intrahepatic - pathology; Biological and medical sciences; Cancer; CDX2 Transcription Factor; Cell cycle; Cell growth; Cholangiocarcinoma - metabolism; Cholangiocarcinoma - pathology; DNA Mutational Analysis; DNA, Neoplasm - genetics; Female; Gallbladder diseases; Gastroenterology. Liver. Pancreas. Abdomen; Gastrointestinal diseases; Gene expression; Genotype & phenotype; Homeodomain Proteins - biosynthesis; Humans; Immunohistochemistry; Kinases; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Middle Aged; Mitogen-Activated Protein Kinase 1 - biosynthesis; Mitogen-Activated Protein Kinase 3 - biosynthesis; Mucin-2; Mucins - biosynthesis; Pharmacology. Drug treatments; Phosphorylation; Proteins; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins B-raf - genetics; Proto-Oncogene Proteins p21(ras); ras Proteins; Tumors
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-006-0129-1

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. 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. 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). 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.