Expression of cyclooxygenase-2 in dysplasia of the stomach and in intestinal-type gastric adenocarcinoma.
OBJECTIVE
Cyclooxygenase (Cox) is the key enzyme in conversion of arachidonic acid to prostanoids. Two Cox genes have been cloned, and expression of Cox-2 mRNA and protein has been shown to be elevated in several human malignancies and in animal models of carcinogenesis. The purpose of this study was to investigate Cox-2 protein expression in human gastric dysplasias and adenocarcinomas.


METHODS
Performance of several Cox-2 antibodies was evaluated, after which Cox-2 protein expression was studied in 67 gastric cancer specimens and in eight definitive dysplasias by using immunohistochemistry.


RESULTS
Cox-2 positivity was detected in 58% (25/43) of the intestinal-type (well-differentiated) tumors and 6% (1/18) of diffuse-type (poorly differentiated) tumors. Consistent with these data, we detected higher expression of Cox-2 mRNA, protein, and enzymatic activity in well-differentiated gastric cancer cell lines (MKN-28 and MKN-74) when compared with poorly differentiated cell lines (HSC-39 and KATO III). Cox-2 immunoreactivity was localized to the carcinoma cells, but the stroma of the tumors was negative. However, strong Cox-2 positivity was consistently detected in stromal cells at sites of erosions and ulcerations. Furthermore, four of nine (44%) definitive dysplasias of the stomach that showed no evidence of invasion were positive for Cox-2.


CONCLUSIONS
Cox-2 is expressed by the neoplastic cells in the intestinal-type gastric adenocarcinoma and by precarcinogenic (dysplastic) lesions leading to this disease.
Saukkonen
K
K
Department of Pathology, Helsinki University Central Hospital, Helsinki, Finland.
Nieminen
O
O
van Rees
B
B
Vilkki
S
S
Härkönen
M
M
Juhola
M
M
Mecklin
J P
JP
Sipponen
P
P
Ristimäki
A
A
D000230:Adenocarcinoma / Q000201:enzymology / Q000473:pathology*; D000328:Adult; D000368:Aged; D051546:Cyclooxygenase 2; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007422:Intestines / Q000473:pathology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013270:Stomach / Q000201:enzymology / Q000473:pathology*; D013274:Stomach Neoplasms / Q000201:enzymology / Q000473:pathology*; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases