Relationship between cyclooxygenase-2 expression and K-ras gene mutation in colorectal adenomas.
OBJECTIVE
Cyclooxygenase (COX)-2 has a trophic effect on gastrointestinal epithelial cells and is associated with the progression of colorectal adenomas. Mutation of the K-ras gene is also associated with the progression of colorectal adenomas and has recently been suggested to play an important role in the induction of COX-2. In the present study, we investigated the relationship between COX-2 expression and K-ras mutation in colorectal adenomas.


METHODS
Twenty-nine colorectal adenomas were obtained from specimens resected by the use of surgery or endoscopic mucosal resection and analyzed clinicopathologically. Immunohistochemistry was performed to analyze COX-2 expression in the adenoma specimens. The K-ras codon 12 mutations were detected by using the polymerase chain reaction-restriction fragment length polymorphism method.


RESULTS
An increase of COX-2-positive cells in adenoma was observed in 11 (37.9%) lesions, 10 (90.9%) of which had a K-ras gene mutation, suggesting a significant correlation between COX-2 expression and K-ras gene mutation in colorectal adenomas. Morphologically, COX-2-positive adenomas (13.8 +/- 2.6 mm) were significantly larger than COX-2-negative ones (5.8 +/- 0.9 mm). In addition, the increase of COX-2-positive cells in the lesion was observed more frequently in tubulovillous (63.6%) than in tubular (36.4%) adenoma.


CONCLUSIONS
Cycloxygenase-2 expression in colorectal adenoma cells is strongly correlated with K-ras gene mutation, suggesting that COX-2 and mutated K-ras are connectively associated with the progression of colorectal adenoma.
Fujita
M
M
Department of Pathology, Dokkyo University School of Medicine, Mibu, Tochigi, Japan.
Fukui
H
H
Kusaka
T
T
Morita
K
K
Fujii
S
S
Ueda
Y
Y
Chiba
T
T
Sakamoto
C
C
Kawamata
H
H
Fujimori
T
T
D000236:Adenoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D051546:Cyclooxygenase 2; D011905:Genes, ras; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D008565:Membrane Proteins; D009154:Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*
D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases