Cyclooxygenase-2 expression in the gallbladder of patients with anomalous arrangement of the pancreaticobiliary duct.
OBJECTIVE
Anomalous arrangement of the pancreaticobiliary duct (AAPBD) is frequently associated with gallbladder carcinoma. Cyclooxygenase (COX) is a key enzyme in the synthesis of prostaglandins, and 2 isoforms have been identified: COX-1 and COX-2. Overexpressed in several precancerous lesions, the COX-2 isoform is thought to be involved in chronic inflammation and carcinogenesis. To determine whether COX expression correlates with biliary histology in patients with AAPBD, the authors investigated the expression of COX-1 and COX-2 in the gallbladder of patients with AAPBD.


METHODS
Gallbladder specimens were obtained from 31 patients with AAPBD (mean age, 5.0 years), and from 7 patients with other hepatobiliary diseases as controls (mean age, 2.0 years). The authors quantified levels of COX-1 and COX-2 by the extent and intensity of staining after immunohistochemistry using anti-COX-1 and anti-COX-2 antibodies.


RESULTS
Mucosal hyperplasia of the gallbladder was identified in 18 of 31 patients with AAPBD. The gallbladder epithelium of all specimens expressed COX-2. Marked expression of COX-2 was noted in specimens with mucosal hyperplasia, the mean immunoreactive score of which was significantly higher than that of specimens without mucosal hyperplasia (7.50 +/- 1.86 and 5.62 +/- 2.26, respectively; P =.021). In contrast, COX-1 expression was not detected in any specimen.


CONCLUSIONS
Enhanced expression of COX-2 is related to mucosal hyperplasia of the gallbladder in patients with AAPBD. Thus, COX-2 may play a regulatory role in the proliferation of gallbladder epithelium, which may lead to carcinogenesis in patients with AAPBD.
Fumino
Shigehisa
S
Division of Surgery, Children's Research Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Tokiwa
Kazuaki
K
Ono
Shigeru
S
Iwai
Naomi
N
D000293:Adolescent; D002277:Carcinoma / Q000209:etiology; D002471:Cell Transformation, Neoplastic; D002648:Child; D002675:Child, Preschool; D002764:Cholecystitis / Q000209:etiology / Q000473:pathology; D003135:Common Bile Duct / Q000002:abnormalities*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D004727:Endothelium / Q000201:enzymology; D004847:Epithelial Cells / Q000201:enzymology; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D005704:Gallbladder / Q000201:enzymology* / Q000473:pathology; D005706:Gallbladder Neoplasms / Q000209:etiology; D006801:Humans; D006965:Hyperplasia; D007527:Isoenzymes / Q000032:analysis*; D008297:Male; D008565:Membrane Proteins; D009092:Mucous Membrane / Q000201:enzymology / Q000473:pathology; D009130:Muscle, Smooth / Q000201:enzymology; D009928:Organ Specificity; D010183:Pancreatic Ducts / Q000002:abnormalities*; D011230:Precancerous Conditions / Q000201:enzymology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis*
D007527:Isoenzymes; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases