Evaluation of matrix metalloproteinase 7 in plasma and pancreatic juice as a biomarker for pancreatic cancer

Koert F.D. Kuhlmann, J. W.Olivier Van Till, Marja A. Boermeester, Philip R. De Reuver, Iva D. Tzvetanova, G. Johan A. Offerhaus, Fiebo J.W. Ten Kate, Olivier R.C. Busch, Thomas M. Van Gulik, Dirk J. Gouma, Howard C. Crawford

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47 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)886-891
Number of pages6
JournalCancer Epidemiology Biomarkers and Prevention
Volume16
Issue number5
DOIs
StatePublished - May 1 2007
Externally publishedYes

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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    Kuhlmann, K. F. D., Van Till, J. W. O., Boermeester, M. A., De Reuver, P. R., Tzvetanova, I. D., Offerhaus, G. J. A., Ten Kate, F. J. W., Busch, O. R. C., Van Gulik, T. M., Gouma, D. J., & Crawford, H. C. (2007). Evaluation of matrix metalloproteinase 7 in plasma and pancreatic juice as a biomarker for pancreatic cancer. Cancer Epidemiology Biomarkers and Prevention, 16(5), 886-891. https://doi.org/10.1158/1055-9965.EPI-06-0779