Cyclooxygenase-2 expression as a new marker for patients with colorectal cancer.
OBJECTIVE
Epidemiologic studies indicate that the use of nonsteroidal anti-inflammatory drugs, which inhibit cyclooxygenase activity, reduce the risk of colorectal cancer. In addition, several studies demonstrate increased expression of cyclooxygenase-2 in human colorectal cancer tissues. However, the role of cyclooxygenase-2 expression in colorectal cancer has not yet been fully established. The aim of this study was to clarify the clinicopathologic significance of cyclooxygenase-2 expression in human colorectal cancer.


METHODS
A total of 232 surgically resected colorectal cancer specimens were analyzed immunohistochemically with the use of a murine anti-human cyclooxygenase-2 monoclonal antibody. Cyclooxygenase-2 expression was then compared with clinicopathologic background and survival outcome.


RESULTS
Cyclooxygenase-2 was expressed in the cytoplasm of the cancer cells but not in normal epithelium. Cyclooxygenase-2 expression was noted in 71.6 percent (166/232) of the cancer patients and correlated significantly with histologic type (P = 0.033), depth of invasion (P = 0.016), pathologic stage (P = 0.020), and metachronous liver metastasis (P = 0.001). Multivariate analysis for factors associated with metachronous liver metastasis showed that cyclooxygenase-2 expression was one of the independent risk factors, second only to lymph node metastasis. Patients with cyclooxygenase-2 expression showed a significantly poorer outcome compared with those without cyclooxygenase-2 expression (P = 0.002).


CONCLUSIONS
Cyclooxygenase-2 expression in the primary lesion may be a useful marker for evaluating prognosis and liver metastasis in patients with colorectal cancer.
Yamauchi
Takeyoshi
T
Department of Pathology, School of Medicine, Keio University, Shinjuku-ku,Tokyo, Japan.
Watanabe
Masahiko
M
Kubota
Tetsuro
T
Hasegawa
Hirotoshi
H
Ishii
Yoshiyuki
Y
Endo
Takashi
T
Kabeshima
Yasuo
Y
Yorozuya
Kyoko
K
Yamamoto
Kentaro
K
Mukai
Makio
M
Kitajima
Masaki
M
D000368:Aged; D000911:Antibodies, Monoclonal / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D051546:Cyclooxygenase 2; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008113:Liver Neoplasms / Q000209:etiology / Q000401:mortality / Q000556:secondary*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D012307:Risk Factors; D015996:Survival Rate
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases