title: LCN2 and TIMP1 as Potential Serum Markers for the Early Detection of Familial Pancreatic Cancer.
abstract: High-risk individuals of familial pancreatic cancer (FPC) families are considered to be good candidates for screening programs to detect early PC or its high-grade precursor lesions, especially pancreatic intraepithelial neoplasia (PanIN) 2/3 lesions. There is a definite need for diagnostic markers as neither reliable imaging methods nor biomarkers are available to detect these lesions. On the basis of a literature search, the potential serum markers neutrophil gelatinase-associated lipocalin (LCN2), metallopeptidase inhibitor 1 (TIMP1), chemokine (C-X-C motif) ligand 16 (CXCL16), IGFBP4, and iC3a, which were first tested in transgenic KrasLSL.(G12D/+);p53(R172H/+);Pdx1-Cre mice, were identified. ELISA analyses of LCN2, TIMP1, and CXCL16 revealed significantly higher levels in mice with PanIN2/3 lesions or PC compared to mice with normal pancreata or PanIN1 lesions. Analysis of preoperative human serum samples from patients with sporadic PC (n = 61), hereditary PC (n = 24), chronic pancreatitis (n = 28), pancreatic neuroendocrine tumors (n = 11), and FPC patients with histologically proven multifocal PanIN2/3 lesions (n = 3), as well as healthy control subjects (n = 20), confirmed significantly higher serum levels of LCN2 and TIMP1 in patients with PC and multifocal PanIN2/3 lesions. The combination of LCN2 and TIMP1 as a diagnostic test for the detection of PC had a sensitivity, specificity, and positive predictive value of 100% each. Although this preliminary finding needs to be validated in a large series of individuals at high risk for FPC, serum measurement of LCN2 and TIMP1 might be a promising screening tool.
authors.affiliation: Department of Surgery, Philipps University, Marburg, Germany.
authors.forename: Emily P
authors.initials: EP
authors.lastname: Slater
authors.forename: Volker
authors.initials: V
authors.lastname: Fendrich
authors.forename: Konstantin
authors.initials: K
authors.lastname: Strauch
authors.forename: Susanne
authors.initials: S
authors.lastname: Rospleszcz
authors.forename: Annette
authors.initials: A
authors.lastname: Ramaswamy
authors.forename: Elvira
authors.initials: E
authors.lastname: Mätthai
authors.forename: Brunhilde
authors.initials: B
authors.lastname: Chaloupka
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Gress
authors.forename: Peter
authors.initials: P
authors.lastname: Langer
authors.forename: Detlef K
authors.initials: DK
authors.lastname: Bartsch
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