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Cyclooxygenase-2 and Cytosolic Phospholipase A2 Are Overexpressed in Mucinous Pancreatic Cysts

Elsie T Mensah1, Thomas Smyrk2, Lizhi Zhang2

  • 1Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.

Clinical and Translational Gastroenterology
|April 23, 2019
PubMed
Abstract

Insights

Cyclooxygenase-2 (COX-2) and cytosolic phospholipase A2 (cPLA2) are overexpressed in mucinous pancreatic cysts. Their inhibition may prevent cyst progression, potentially requiring higher aspirin (ASA) doses.

Area of Science:

  • Gastroenterology
  • Oncology
  • Biochemistry

Background:

  • The expression of enzymes in the prostaglandin biosynthetic pathway within mucinous pancreatic cysts is not well understood.
  • Cyclooxygenase-2 (COX-2) inhibition presents a potential strategy for cancer chemoprevention in these lesions.

Purpose of the Study:

  • To evaluate the expression of COX-2, cytosolic phospholipase A2 (cPLA2), and protein kinase B (AKT) in pancreatic cyst epithelium.
  • To correlate enzyme expression with aspirin (ASA) use and cyst fluid prostaglandin E2 (PGE2) levels.

Main Methods:

  • Review of pathology from 80 resected pancreatic cysts.
  • Quantification of COX-2, cPLA2, and AKT expression using immunohistochemistry immunoreactivity scores (IRSs).
  • Comparison of IRS values between cyst types and with cyst fluid PGE2 concentrations.

Main Results:

  • Mucinous cysts showed significantly higher COX-2 and cPLA2 expression compared to nonmucinous cysts.
  • COX-2 expression was higher in low-grade dysplasia mucinous cysts, while cPLA2 was higher in high-grade dysplasia or invasive carcinoma.
  • Cyst fluid PGE2 levels did not correlate with enzyme expression or low- to moderate-dose ASA use.

Conclusions:

  • COX-2 and cPLA2 are overexpressed in mucinous pancreatic cysts.
  • Inhibition of COX-2 and/or cPLA2 may prevent the development or progression of these cysts.
  • Higher doses of aspirin or NSAIDs might be needed to effectively inhibit cyst epithelial COX-2 activity.

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