EGFR and HER2 expression in advanced biliary tract cancer

AIM:To analyze the pathogenetic role and potential clinical usefulness of the epidermal growth factor receptor(EGFR)and the human epidermal growth factor receptor 2(HER2)in patients with advanced biliary tract cancer(BTC). METHODS:EGFR and HER2 expression was studied in biopsy samples from 124 patients(51%women; median age 64.8 years),with advanced BTC diagnosed between 1997 and 2004.Five micrometers sections of paraffin embedded tissue were examined by standard, FDA approved immunohistochemistry.Tumors with scores of 2+or 3+for HER2 expression on immunochemistry were additionally tested for HER2 gene amplification by fluorescence in situ hybridisation(FISH).RESULTS:34/124 patients(27.4%)had gallbladder cancer,47(37.9%)had intrahepatic BTC and 43(34.7%)had extrahepatic or perihilar BTC.EGFR expression was examined in a subset of 56 samples. EGFR expression was absent in 22/56 tumors(39.3%). Of the remaining samples expression was scored as 1+in 12(21.5%),2+in 13(23.2%)and 3+in 9(16%), respectively.HER2 expression was as follows:score 0 73/124(58.8%),score 1+27/124(21.8%),score 2+ 21/124(17%)and score 3+4/124(3.2%).HER2 gene amplification was present in 6/124,resulting in an overall amplification rate of 5%. CONCLUSION:Our data suggest that routine testing and therapeutic targeting of HER2 does not seem to be useful in patients with BTC,while targeting EGFR may be promising.

Effects of warm ischemia time on biliary injury in rat liver transplantation

AIM:To investigate the effect of different secondary warm ischemia time (SWIT) on bile duct injury in livertransplanted rats. METHODS:Forty-eight male inbred Sprague-Dawley rats were randomly assigned into four groups:a shamoperation group and three groups with secondary biliary warm ischemia time of 0 min, 10 min and 20 min. A rat model of autologous liver transplantation under ether anesthesia was established, and six rats were killed in each group and blood samples and the median lobe of the liver were collected for assay at 6 h and 24 h after hepatic arterial reperfusion. RESULTS:With prolongation of biliary warm ischemia time, the level of vascular endothelial growth factor-A was significantly decreased, and the value at 24 h was higher than that at 6 h after hepatic arterial reperfusion, but with no significant difference. The extended biliary SWIT led to a significant increase in bile duct epithelial cell apoptosis, and a decrease in the number of blood vessels, the bile duct surrounding the blood vessels and bile duct epithelial cell proliferation in the early postoperative portal area. Pathologic examinations showed that inflammation of the rat portal area was aggravated, and biliary epithelial cell injury was significantly worsened. CONCLUSION:A prolonged biliary warm ischemia time results in aggravated injury of the bile duct and the surrounding vascular plexus in rat autologous orthotopic liver transplantation.

There is no association between K469E ICAM-1 gene polymorphism and biliary atresia

AIM： To determine whether there was an association between inter-cellular adhesion molecule-1 （ICAM-1） gene polymorphism and biliary atresia （BA）, and to investigate the relationship between serum soluble ICAM-1 （sICAM-1） and clinical outcome in BA patients after surgical treatment, METHODS： Eighty-three BA patients and 115 normal controls were genotyped. K469EICAM-1 polymorphism was analyzed using PCR assay. Serum sICAM-1 was determined using ELISA rnebhod from 72 BA patients. In order to evaluate the association between these variables and their clinical outcome, the patients were categorized into two groups： patients without jaundice and those with persistent jaundice. RESULTS： There were no significant differences between BA patients and controls in terms of gender, K469E ICAM-1 genotypes, and alleles. The proportion of patients having serum sICAM-1 ≥3 500 ng/mL in persistent jaundice group was significantly higher than that in the other group. In addition, there was no association between K469EICAM-1 polymorphism and the status of jaundice in BA patients after Kasai operation. CONCLUSION： ICAM-1 possibly plays an important and active role in the disease progression. However, the process is not associated with genetic variation of K469E ICAM-1 polymorphism.