Cyclooxygenase 2 expression in pancreatic adenocarcinoma and pancreatic intraepithelial neoplasia: an immunohistochemical analysis with automated cellular imaging.
We immunohistochemically examined material from 36 pancreata (adenocarcinomas, 30 lesions; pancreatic intraepithelial neoplasia [PanIN], 65; normal pancreatic ducts, 30) for cyclooxygenase 2 (COX-2) with an automated platform. We analyzed 7 to 10 discrete foci and generated an average percentage of positive cells and average staining intensity for each lesion. These 2 values were then multiplied to create an overall "HistoScore" for each lesion. COX-2 demonstrated considerable heterogeneity of expression between and within cases. The overall average percentage of positive cells in adenocarcinomas was 47.3%; in PanINs, 36.3%; and in normal ducts, 19.2%. COX-2 was expressed in more than 20% of cells in 23 adenocarcinomas (77%), 42 PanINs (65%), and 12 normal ducts (40%). The overall average HistoScore for adenocarcinomas was 6.1; for PanINs, 5.4; and for normal ducts, 3.5. Significant differences in COX-2 expression were demonstrable in adenocarcinomas vs normal ducts, PanINs vs normal ducts, and PanIN 2/3 vs PanIN 1a/1b. In general, the pattern of COX-2 expression increased from normal to PanIN to adenocarcinoma. The up-regulation of COX-2 in a subset of noninvasive precursor lesions makes it a potential target for chemoprevention with selective COX-2 inhibitors.
Maitra
Anirban
A
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.
Ashfaq
Raheela
R
Gunn
Carla R
CR
Rahman
Ayman
A
Yeo
Charles J
CJ
Sohn
Taylor A
TA
Cameron
John L
JL
Hruban
Ralph H
RH
Wilentz
Robb E
RE
D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002278:Carcinoma in Situ / Q000201:enzymology* / Q000473:pathology; D051546:Cyclooxygenase 2; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000473:pathology; D011230:Precancerous Conditions / Q000201:enzymology / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*
D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases