title: Evaluation of matrix metalloproteinase 7 in plasma and pancreatic juice as a biomarker for pancreatic cancer.
abstract: Differentiating between periampullary carcinoma and chronic pancreatitis with an inflammatory mass is difficult. Consequently, 6% to 9% of pancreatic resections for suspected carcinoma are done inappropriately for chronic pancreatitis. Here, we test if matrix metalloproteinase 7 (MMP-7), a secreted protease frequently expressed in pancreatic carcinoma, can be measured in plasma, pancreatic, and duodenal juice, and if it can distinguish between periampullary carcinoma and chronic pancreatitis. Ninety-four patients who underwent pancreatic surgery for a (peri)pancreatic neoplasm (n = 63) or chronic pancreatitis (n = 31) were analyzed. Median plasma MMP-7 levels were significantly higher in carcinoma (1.95 ng/mL; interquartile range, 0.81-3.22 ng/mL) compared with chronic pancreatitis and benign disease (0.83 ng/mL; interquartile range, 0.25-1.21 ng/mL; P < 0.01). MMP-7 levels in pancreatic juice were higher, although not significantly, in carcinoma (62 ng/mg protein; interquartile range, 18-241 ng/mg protein) compared with chronic pancreatitis and benign disease (23 ng/mg protein; interquartile range, 8.5-99 ng/mg protein; P = 0.17). MMP-7 levels in duodenal juice were universally low. At an arbitrary cutoff of 1.5 ng/mL in plasma, positive and negative predictive values were 83% and 57%, respectively, values comparable to those of today's most common pancreatic tumor marker, carbohydrate antigen 19-9 (CA19-9; 83% and 53%, respectively). Positive and negative likelihood ratios for plasma MMP-7 were 3.35 and 0.52, respectively. The area under the receiver operating characteristic curve for MMP-7 was 0.73 (95% confidence interval, 0.63-0.84) and for CA19-9, 0.75 (95% confidence interval, 0.64-0.85). Combined MMP-7 and CA19-9 assessment gave a positive predictive value of 100%. Thus, plasma MMP-7 levels discriminated between patients with carcinoma and those with chronic pancreatitis or benign disease. The diagnostic accuracy of plasma MMP-7 alone is not sufficient to determine treatment strategy in patients with a periampullary mass, but combined evaluation of plasma MMP-7 with CA19-9 and other markers may be clinically useful.
authors.affiliation: Department of Surgery, Academic Medical Center of the University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Koert F D
authors.initials: KF
authors.lastname: Kuhlmann
authors.forename: J W Olivier
authors.initials: JW
authors.lastname: van Till
authors.forename: Marja A
authors.initials: MA
authors.lastname: Boermeester
authors.forename: Philip R
authors.initials: PR
authors.lastname: de Reuver
authors.forename: Iva D
authors.initials: ID
authors.lastname: Tzvetanova
authors.forename: G Johan A
authors.initials: GJ
authors.lastname: Offerhaus
authors.forename: Fiebo J W
authors.initials: FJ
authors.lastname: Ten Kate
authors.forename: Olivier R C
authors.initials: OR
authors.lastname: Busch
authors.forename: Thomas M
authors.initials: TM
authors.lastname: van Gulik
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Gouma
authors.forename: Howard C
authors.initials: HC
authors.lastname: Crawford
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000097:blood; D018395:CA-19-9 Antigen / Q000097:blood; D002277:Carcinoma / Q000097:blood / Q000175:diagnosis*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000032:analysis* / Q000097:blood; D008875:Middle Aged; D010189:Pancreatic Juice / Q000201:enzymology*; D010190:Pancreatic Neoplasms / Q000097:blood / Q000175:diagnosis*; D050500:Pancreatitis, Chronic / Q000175:diagnosis; D012372:ROC Curve
chemical_list: D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D020783:Matrix Metalloproteinase 7