Immunohistochemical Expression of Insulin-Like Growth Factor (IGF) Messenger Binding Protein-3 (IMP-3), S100A4 and CDX2 in Intrahepatic Cholangiocarcinoma (IHCC) and Extrahepatic Cholangiocarcinoma (EHCC) Cholangiocarcinoma and their Potential Biological Value.
Cecilia E Gimenez, Soma G Karak, Daniza Mandich, Richard Cartun, Saverio Ligato. Hartford Hospital, CT
Background: Cholangiocarcinomas (CC) originate from the bile duct epithelium in either intrahepatic or extrahepatic location. In the development of the human biliary system, the extrahepatic bile ducts (EHBD) develop from the embryonic hepatic diverticulum, while the intrahepatic bile ducts (IHBD) originate within the liver from the ductal plate.
Due to this different embryological origin, we postulate that there is also a different immunohistochemical expression of certain markers between the intrahepatic cholangiocarcinomas (IHCC) and extrahepatic cholangiocarcinoma (EHCC). Previous studies have demonstrated an immunohistochemical expression of IMP-3 (also known as KOC), S100A4, and CDX2 in both pancreatic carcinoma and extrahepatic cholangiocarcinoma but no study has examined their expression in terms of IHCC versus EHCC.
Our aim is to investigate the immunophenotype of IHCC and EHCC and to find out new markers for their classification and different biological origin.
Design: We collected 19 cases of cholangiocarcinoma (CC), subdivided into 11 cases of IHCC and 8 cases of EHCC. All cases were immunohistochemicaly analyzed for IMP3 (KOC/L523S clone 69:1 Dako), S100A4 (Dabo polyclonal) and CDX 2 (Biogenex clone: CDX2-88) expression. The antibodies were estimated semiquantitatively: negative (-) if <5%, positive cells, grade 1 (+) between 5 and 20%, grade 2(++) between 20 and 50% and 3 (+++) >50%.
Results: EHCC expressed IMP-3 in 6/8 (75%), S100A4 in 4/8(50%), and CDX2 in 2/8(25%). IHCC expressed IMP-3 in 2/11(18%), S100A4 in 4/11(36%), CDX2 in 0/11(0%). Of all markers studied only the expression of IMP-3 was statistically significant (p<0.02).
|IHCC||2/11 (18%)||4/11 (36%)||0/11 (0%)|
|EHCC||6/8 (75%)||4/8 (50%)||2/8 (25%|