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Reversal of expression of 15‐lipoxygenase‐1 to cyclooxygenase‐2 is associated with development of colonic cancer
Author(s) -
Yuri M,
Sasahira T,
Nakai K,
Ishimaru S,
Ohmori H,
Kuniyasu H
Publication year - 2007
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/j.1365-2559.2007.02799.x
Subject(s) - adenoma , immunohistochemistry , cyclooxygenase , carcinoma , pathology , colorectal cancer , medicine , cancer , cancer research , biology , endocrinology , enzyme , biochemistry
Aims: Two different pathways of linoleic acid (LA) metabolism have opposite effects on the development of colonic cancer: a protumoral prostaglandin cascade metabolized by cyclooxygenase (COX)‐2, and an antitumoral peroxisome proliferator‐activated receptor (PPAR)‐γ ligands metabolized by 15‐lipooxygenase (LOX)‐1. The aim was to examine the switching of the two LA metabolic pathways in colonic adenomas and carcinomas. Materials and methods: The expression of 15LOX‐1 mRNA and COX‐2 protein was examined in 54 adenomas, 21 pTis carcinoma‐in‐adenoma lesions and 36 pT3/p Stage II carcinomas of the colon by in‐situ hybridization and immunohistochemistry, respectively. Results: 15LOX‐1 expression was found in 89% (48 of 54) of adenomas, 43% (nine of 21) of adenomas and 10% (two of 21) of carcinomas in carcinoma‐in‐adenoma lesions, but not in pT3 carcinomas ( P < 0.0001). In contrast, COX‐2 production was found in 11% (six of 54) of adenomas, 52% (11 of 21) of adenomas and 71% (15 of 21) of carcinomas in carcinoma‐in‐adenoma lesions, and 92% (33 of 36) of pT3 carcinomas ( P < 0.0001). Concurrence of 15LOX‐1 down‐regulation and COX‐2 up‐regulation was found in 6% (three of 54) of adenomas, 33% (seven of 21) of adenomas and 71% (15 of 21) of carcinomas in carcinoma‐in‐adenoma lesions, and 92% (33 of 36) of pT3 carcinomas ( P < 0.0001). Conclusions: These results suggest that switching of LA metabolism by reversal of the expression of 15LOX‐1 and COX‐2 is associated with acquisition of malignant potential in colonic neoplasia.