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

环氧合酶-2 和胞浆磷脂酶 A2 在粘液性胰腺囊肿中过度表达

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

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.

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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