title: Measurement of serum carcinoembryonic antigen, carbohydrate antigen 19-9, cytokeratin-19 fragment and matrix metalloproteinase-7 for detecting cholangiocarcinoma: a preliminary case-control study.
abstract: Cholangiocarcinoma is a malignant tumor of the liver arising from the bile duct epithelium, accounting for 10-25% of all primary hepatic cancers. The clinical presentation of this tumor is not specific and the diagnosis of early cholangiocarcinoma is difficult, especially in patients with other biliary diseases. Measurement of serum carbohydrate antigen (CA) 19-9 and carcinoembryonic antigen (CEA) are commonly used to monitor response to therapy, but are also useful for confirming the presence of a cholangiocarcinoma. In this setting, other biomarkers have been previously tested, including cytokeratin-19 fragment (CYFRA 21-1) and the matrix metalloproteinase-7 (MMP7). The purpose of this retrospective study was to determine the clinical usefulness of the assay of serum CEA, CA 19-9, CYFRA 21-1 and MMP7, individually and together, as tumor markers for the diagnosis of cholangiocarcinoma. Twenty-four patients (14 men, 10 women, 62.6±8.2 years of age) with histologically-confirmed cholangiocarcinoma (cases) and 25 age- and sex-matched patients with benign liver disease (controls) underwent measurement of these biomarkers. The mean values of all serum markers of patients with cholangiocarcinoma were significantly higher (p<0.01) than that of the controls. No correlation was found between serum tumor markers and total bilirubin, aspartate aminotransferase (AST) and alkaline phosphatase (ALP). The sensitivity, specificity and accuracy were: CEA: 52%, 55%, and 58%; CA 19-9: 74%, 82% and 78%; CYFRA 21-1: 76%, 79% and 78%; MMP7: 78%, 77% and 80%, respectively. The combination of all serum markers afforded 92.0% sensitivity and 96% specificity in detecting cholangiocarcinoma, showing the highest diagnostic accuracy (94%). In conclusion, our preliminary results suggest that the measurement of all four biomarkers together can help in the early detection of cholangiocarcinoma.
authors.affiliation: Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padua, School of Medicine, Padova, Italy flumachi@unipd.it.
authors.forename: Franco
authors.initials: F
authors.lastname: Lumachi
authors.affiliation: Medical Oncology, S. Maria degli Angeli Hospital, Pordenone, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Lo Re
authors.affiliation: Clinical Pathology, S. Maria degli Angeli Hospital, Pordenone, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Tozzoli
authors.affiliation: Clinical Pathology, S. Maria degli Angeli Hospital, Pordenone, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: D'Aurizio
authors.affiliation: Clinical Pathology, S. Maria degli Angeli Hospital, Pordenone, Italy.
authors.forename: Flavio
authors.initials: F
authors.lastname: Facomer
authors.affiliation: Surgery 1, S. Maria degli Angeli Hospital, Pordenone, Italy.
authors.forename: Giordano B
authors.initials: GB
authors.lastname: Chiara
authors.affiliation: Surgery 1, S. Maria degli Angeli Hospital, Pordenone, Italy.
authors.forename: Stefano M M
authors.initials: SM
authors.lastname: Basso
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000097:blood*; D001650:Bile Duct Neoplasms / Q000097:blood* / Q000175:diagnosis; D001653:Bile Ducts, Intrahepatic / Q000473:pathology; D014408:Biomarkers, Tumor / Q000097:blood*; D018395:CA-19-9 Antigen / Q000097:blood*; D002272:Carcinoembryonic Antigen / Q000097:blood*; D016022:Case-Control Studies; D018281:Cholangiocarcinoma / Q000097:blood* / Q000175:diagnosis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053539:Keratin-19 / Q000097:blood*; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000097:blood*; D008875:Middle Aged; D011379:Prognosis; D012372:ROC Curve; D012189:Retrospective Studies
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D002272:Carcinoembryonic Antigen; D053539:Keratin-19; C102012:antigen CYFRA21.1; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7
keywords: CA 19-9; CEA; CYFRA 21-1; Cholangiocarcinoma; MMP7; diagnosis; serum tumor marker