Several studies have demonstrated overexpression of the epidermal growth factor receptor (EGFR) in CCA cells. EGFR is a type 1 tyrosine kinase promoting cell proliferation, migration and altered cell adhesion - typical characteristics of malignant neoplasias. In CCA cells, EGFR-activation is sustained resulting in cancer progression. In human CCA samples, EGFR-expression correlates with higher histologic grade, poor prognosis, and risk of recurrence. The EGFR gene is located on the short arm of chromosome 7 (7p12). Chromosomal abnormalities of the bile duct epithelium, particularly trisomy 7 (i.e. three copies of chromosome 7) can be detected in biliary epithelial samples obtained by endoscopic retrograde cholangiopancreatography (ERCP) in PSC patients. The finding of cells with trisomy 7 has preceded the development of aneuploidy and multiple chromosomal abnormalities in a number of patients, the latter chromosomal abnormalities are characteristic of CCA. Trisomy 7 amplifies the gene for EGFR thereby presumably promoting overexpression of this growth factor receptor. In a cohort of patients with Trisomy 7 and Primary Sclerosing Cholangitis patients followed for 1 year, the rate of development of Cholangiocarcinoma was 35% (n=37, Dr. Gores, unpublished observation). Patients without cytologic abnormalities were at minimal risk for the development of CCA.