Cyclooxygenase-2 expression associated with severity of PanIN lesions: a possible link between chronic pancreatitis and pancreatic cancer.
BACKGROUND
Cyclooxygenase-2 (COX-2) is a key modulatory molecule in inflammation and neoplasia. Increasing evidence suggests a role for COX-2 in pancreatic cancer (PAC). However, expression of COX-2 in pancreatic intraepithelial neoplasia (PanIN), the precursor lesion of PAC which is often present in chronic pancreatitis (CP), has received little attention.


METHODS
COX-2 immunostaining was performed on sections of PAC (n = 26), CP (n = 34), PanIN (n = 68) and normal pancreas (n = 11). Sections were also stained for macrophages (CD68), activated pancreatic stellate cells (alphaSMA), and collagen (Sirius Red) as markers of fibrosis. Semiquantitative scoring was based on the extent and intensity of immunostaining.


RESULTS
COX-2 expression was increased in PAC compared to normal (p = 0.02) with 89% of cases exceeding COX-2 immunostaining in normal ducts. In PanIN lesions, COX-2 expression increased with escalating severity of the PanIN change (p < or = 0.01). COX-2 expression was increased in PanIN-2/3 compared to normal pancreas and CP (p < or = 0.001). In ducts of CP, COX-2 expression did not differ from that in normal tissue. There was no association between COX-2 expression and clinicopathological variables.


CONCLUSIONS
The high level of COX-2 expression in PanIN lesions suggests that this enzyme could be a therapeutic target at a non-invasive stage of pancreatic carcinogenesis and feasible for chemoprevention in CP.
Academic Unit of Surgery, The General Infirmary at Leeds, St James's University Hospital, Leeds, UK.
R
R
Albazaz
C S
CS
Verbeke
S H
SH
Rahman
M J
MJ
McMahon
D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002278:Carcinoma in Situ / Q000201:enzymology* / Q000473:pathology; D002452:Cell Count; D002908:Chronic Disease; D051546:Cyclooxygenase 2; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D010179:Pancreas / Q000033:anatomy & histology / Q000201:enzymology / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000473:pathology; D010195:Pancreatitis / Q000201:enzymology* / Q000473:pathology; D011230:Precancerous Conditions / Q000201:enzymology* / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*
D015415:Biomarkers; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases