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

Elsie T. Mensah, Thomas Christopher Smyrk, Lizhi Zhang, Benjamin Bick, Christina M. Wood-Wentz, Navtej Singh Buttar, Suresh T Chari, Ferga C. Gleeson, Michael Kendrick, Michael Levy, Randall Pearson, Bret Thomas Petersen, Santhi Swaroop Vege, Felicity T Enders, Paul John Limburg, Mark Topazian

Research output: Contribution to journalArticle

Abstract

OBJECTIVES: Expression of prostaglandin biosynthetic pathway enzymes in mucinous pancreatic cysts is unknown. Cyclooxygenase-2 (COX-2) inhibition is a potential cancer chemoprevention strategy for these lesions. We evaluated the expression of COX-2, cytosolic phospholipase A2 (cPLA2), and protein kinase B (AKT) in the epithelium of pancreatic cysts and correlated enzyme expression with aspirin (ASA) use and cyst fluid prostaglandin E2 (PGE2) concentration. METHODS: Pathology of 80 resected pancreatic cysts was reviewed. Expression of COX-2, cPLA2, and AKT was quantified by tissue immunohistochemistry immunoreactivity scores (IRSs). IRS values were compared between cyst types and (in 30 cases) with matched cyst fluid PGE2 concentrations. RESULTS: The mean IRS was higher in the epithelium of mucinous vs nonmucinous cysts for COX-2 (6.1 ± 4.7 vs 3.2 ± 2.8, P = 0.01) and cPLA2 (6.9 ± 3.0 vs 2.9 ± 2.9, P < 0.001). Cyst epithelial COX-2 expression was higher in mucinous cysts with low-grade dysplasia vs those with high-grade dysplasia or invasive carcinoma (IRS 8.0 ± 3.9 vs 1.5 ± 2.9, P < 0.001), whereas the opposite was found for cPLA2 (6.2 ± 3.0 vs 8.6 ± 2.3, P = 0.005). Cyst fluid PGE2 concentrations did not correlate with either the IRS or a history of low- to moderate-dose ASA use. CONCLUSIONS: COX-2 and cPLA2 are overexpressed in the epithelium of mucinous pancreatic cysts. COX-2 and/or cPLA2 inhibition might prevent the emergence or progression of mucinous pancreatic cysts, but higher doses of ASA or nonsteroidal anti-inflammatory drugs may be necessary to substantially inhibit cyst epithelial COX-2 activity.

Original languageEnglish (US)
Pages (from-to)e00028
JournalClinical and translational gastroenterology
Volume10
Issue number4
DOIs
StatePublished - Apr 1 2019

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Pancreatic Cyst
Cytosolic Phospholipases A2
Cyclooxygenase 2
Cysts
Cyst Fluid
Dinoprostone
Epithelium
Proto-Oncogene Proteins c-akt
Biosynthetic Pathways
Chemoprevention
Enzymes
Aspirin
Prostaglandins
Anti-Inflammatory Agents
Immunohistochemistry
Pathology
Carcinoma

ASJC Scopus subject areas

  • Gastroenterology

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Cyclooxygenase-2 and Cytosolic Phospholipase A2 Are Overexpressed in Mucinous Pancreatic Cysts. / Mensah, Elsie T.; Smyrk, Thomas Christopher; Zhang, Lizhi; Bick, Benjamin; Wood-Wentz, Christina M.; Buttar, Navtej Singh; Chari, Suresh T; Gleeson, Ferga C.; Kendrick, Michael; Levy, Michael; Pearson, Randall; Petersen, Bret Thomas; Vege, Santhi Swaroop; Enders, Felicity T; Limburg, Paul John; Topazian, Mark.

In: Clinical and translational gastroenterology, Vol. 10, No. 4, 01.04.2019, p. e00028.

Research output: Contribution to journalArticle

Mensah, Elsie T. ; Smyrk, Thomas Christopher ; Zhang, Lizhi ; Bick, Benjamin ; Wood-Wentz, Christina M. ; Buttar, Navtej Singh ; Chari, Suresh T ; Gleeson, Ferga C. ; Kendrick, Michael ; Levy, Michael ; Pearson, Randall ; Petersen, Bret Thomas ; Vege, Santhi Swaroop ; Enders, Felicity T ; Limburg, Paul John ; Topazian, Mark. / Cyclooxygenase-2 and Cytosolic Phospholipase A2 Are Overexpressed in Mucinous Pancreatic Cysts. In: Clinical and translational gastroenterology. 2019 ; Vol. 10, No. 4. pp. e00028.
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abstract = "OBJECTIVES: Expression of prostaglandin biosynthetic pathway enzymes in mucinous pancreatic cysts is unknown. Cyclooxygenase-2 (COX-2) inhibition is a potential cancer chemoprevention strategy for these lesions. We evaluated the expression of COX-2, cytosolic phospholipase A2 (cPLA2), and protein kinase B (AKT) in the epithelium of pancreatic cysts and correlated enzyme expression with aspirin (ASA) use and cyst fluid prostaglandin E2 (PGE2) concentration. METHODS: Pathology of 80 resected pancreatic cysts was reviewed. Expression of COX-2, cPLA2, and AKT was quantified by tissue immunohistochemistry immunoreactivity scores (IRSs). IRS values were compared between cyst types and (in 30 cases) with matched cyst fluid PGE2 concentrations. RESULTS: The mean IRS was higher in the epithelium of mucinous vs nonmucinous cysts for COX-2 (6.1 ± 4.7 vs 3.2 ± 2.8, P = 0.01) and cPLA2 (6.9 ± 3.0 vs 2.9 ± 2.9, P < 0.001). Cyst epithelial COX-2 expression was higher in mucinous cysts with low-grade dysplasia vs those with high-grade dysplasia or invasive carcinoma (IRS 8.0 ± 3.9 vs 1.5 ± 2.9, P < 0.001), whereas the opposite was found for cPLA2 (6.2 ± 3.0 vs 8.6 ± 2.3, P = 0.005). Cyst fluid PGE2 concentrations did not correlate with either the IRS or a history of low- to moderate-dose ASA use. CONCLUSIONS: COX-2 and cPLA2 are overexpressed in the epithelium of mucinous pancreatic cysts. COX-2 and/or cPLA2 inhibition might prevent the emergence or progression of mucinous pancreatic cysts, but higher doses of ASA or nonsteroidal anti-inflammatory drugs may be necessary to substantially inhibit cyst epithelial COX-2 activity.",
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T1 - Cyclooxygenase-2 and Cytosolic Phospholipase A2 Are Overexpressed in Mucinous Pancreatic Cysts

AU - Mensah, Elsie T.

AU - Smyrk, Thomas Christopher

AU - Zhang, Lizhi

AU - Bick, Benjamin

AU - Wood-Wentz, Christina M.

AU - Buttar, Navtej Singh

AU - Chari, Suresh T

AU - Gleeson, Ferga C.

AU - Kendrick, Michael

AU - Levy, Michael

AU - Pearson, Randall

AU - Petersen, Bret Thomas

AU - Vege, Santhi Swaroop

AU - Enders, Felicity T

AU - Limburg, Paul John

AU - Topazian, Mark

PY - 2019/4/1

Y1 - 2019/4/1

N2 - OBJECTIVES: Expression of prostaglandin biosynthetic pathway enzymes in mucinous pancreatic cysts is unknown. Cyclooxygenase-2 (COX-2) inhibition is a potential cancer chemoprevention strategy for these lesions. We evaluated the expression of COX-2, cytosolic phospholipase A2 (cPLA2), and protein kinase B (AKT) in the epithelium of pancreatic cysts and correlated enzyme expression with aspirin (ASA) use and cyst fluid prostaglandin E2 (PGE2) concentration. METHODS: Pathology of 80 resected pancreatic cysts was reviewed. Expression of COX-2, cPLA2, and AKT was quantified by tissue immunohistochemistry immunoreactivity scores (IRSs). IRS values were compared between cyst types and (in 30 cases) with matched cyst fluid PGE2 concentrations. RESULTS: The mean IRS was higher in the epithelium of mucinous vs nonmucinous cysts for COX-2 (6.1 ± 4.7 vs 3.2 ± 2.8, P = 0.01) and cPLA2 (6.9 ± 3.0 vs 2.9 ± 2.9, P < 0.001). Cyst epithelial COX-2 expression was higher in mucinous cysts with low-grade dysplasia vs those with high-grade dysplasia or invasive carcinoma (IRS 8.0 ± 3.9 vs 1.5 ± 2.9, P < 0.001), whereas the opposite was found for cPLA2 (6.2 ± 3.0 vs 8.6 ± 2.3, P = 0.005). Cyst fluid PGE2 concentrations did not correlate with either the IRS or a history of low- to moderate-dose ASA use. CONCLUSIONS: COX-2 and cPLA2 are overexpressed in the epithelium of mucinous pancreatic cysts. COX-2 and/or cPLA2 inhibition might prevent the emergence or progression of mucinous pancreatic cysts, but higher doses of ASA or nonsteroidal anti-inflammatory drugs may be necessary to substantially inhibit cyst epithelial COX-2 activity.

AB - OBJECTIVES: Expression of prostaglandin biosynthetic pathway enzymes in mucinous pancreatic cysts is unknown. Cyclooxygenase-2 (COX-2) inhibition is a potential cancer chemoprevention strategy for these lesions. We evaluated the expression of COX-2, cytosolic phospholipase A2 (cPLA2), and protein kinase B (AKT) in the epithelium of pancreatic cysts and correlated enzyme expression with aspirin (ASA) use and cyst fluid prostaglandin E2 (PGE2) concentration. METHODS: Pathology of 80 resected pancreatic cysts was reviewed. Expression of COX-2, cPLA2, and AKT was quantified by tissue immunohistochemistry immunoreactivity scores (IRSs). IRS values were compared between cyst types and (in 30 cases) with matched cyst fluid PGE2 concentrations. RESULTS: The mean IRS was higher in the epithelium of mucinous vs nonmucinous cysts for COX-2 (6.1 ± 4.7 vs 3.2 ± 2.8, P = 0.01) and cPLA2 (6.9 ± 3.0 vs 2.9 ± 2.9, P < 0.001). Cyst epithelial COX-2 expression was higher in mucinous cysts with low-grade dysplasia vs those with high-grade dysplasia or invasive carcinoma (IRS 8.0 ± 3.9 vs 1.5 ± 2.9, P < 0.001), whereas the opposite was found for cPLA2 (6.2 ± 3.0 vs 8.6 ± 2.3, P = 0.005). Cyst fluid PGE2 concentrations did not correlate with either the IRS or a history of low- to moderate-dose ASA use. CONCLUSIONS: COX-2 and cPLA2 are overexpressed in the epithelium of mucinous pancreatic cysts. COX-2 and/or cPLA2 inhibition might prevent the emergence or progression of mucinous pancreatic cysts, but higher doses of ASA or nonsteroidal anti-inflammatory drugs may be necessary to substantially inhibit cyst epithelial COX-2 activity.

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