Correlation between cyclooxygenase-2, proliferative activity, and mucin phenotype in human advanced gastric cancer.
BACKGROUND
Recent studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the risk of gastrointestinal cancer, and that cyclooxygenase-2 (COX-2) may be a target enzyme for the prevention or regression of cancer by the use of NSAIDs. Mucin histochemistry has made possible a clear distinction between the differentiated characteristics of gastrointestinal epithelial cells, and the possibility that phenotypic shifts from gastric- to intestinal-type in gastric carcinoma progression has been suggested. To evaluate the role of COX-2 in gastric cancer progression, we immunohistochemically investigated COX-2 expression, and examined its relationship to proliferative activity, mucin phenotype, and clinicopathological parameters in human advanced gastric carcinomas.


METHODS
Forty-five surgical specimens of advanced gastric carcinomas (invaded the muscularis propria or subserosa) were examined. Immunohistochemical staining was performed with monoclonal antibodies against COX-2, Ki-67, CD10 (brush border), MUC-2 (goblet-cell mucin), MUC-5AC (gastric foveolar mucin), and MUC-6 (pyloric mucin). COX-2 expression was scored by the percentage of COX-2-positive neoplastic cells, and proliferative activity was assessed by the Ki-67 labeling index at the deepest area of invasion. The mucin phenotype of the carcinomas was classified into three categories; gastric, intestinal, and unclassified.


RESULTS
COX-2 staining was restricted to the cytoplasm, not only in cancer cells but also in intestinal metaplasia and some inflammatory cells and COX-2 expression in cancer cells varied greatly, but the staining in some samples was preferentially found at the invasive front. COX-2 positivity was found to correlate with Ki-67 labeling. The mean COX-2 scores were 2.29%, 2.71%, and 2.75%; and the Ki-67 labeling indices were 23.6%, 40.6%, and 56.5%, in gastric-, intestinal-, and unclassified- type carcinomas, respectively.


CONCLUSIONS
A close relationship between COX-2 expression and proliferative activity was confirmed in the deepest areas of advanced gastric carcinoma, and the proliferative activity increased from gastric- to intestinal- and to unclassified- type gastric carcinoma, suggesting a role for COX-2 expression and differences in biological behavior according to mucin phenotype expression during gastric cancer progression.
Yamagishi
Mariko
M
Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
Noda
Masao
M
Tatsumi
Yoichi
Y
Mukaisho
Ken-ichi
K
Mitsufuji
Shoji
S
Sugihara
Hiroyuki
H
Okanoue
Takeshi
T
Hattori
Takanori
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002455:Cell Division; D051546:Cyclooxygenase 2; D018450:Disease Progression; D006801:Humans; D008565:Membrane Proteins; D008875:Middle Aged; D009077:Mucins / Q000235:genetics*; D010641:Phenotype; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology
D008565:Membrane Proteins; D009077:Mucins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases