Aberrant methylation of cyclooxygenase-2 in breast cancer patients.
BACKGROUND
Although aberrant CpG island methylation and subsequent silencing of the cyclooxygenase-2 (COX-2) promoter has been observed in colorectal and gastric tumors recently, little is known about that in breast cancers. The aim of this study was to identify the methylation status of COX-2 as well as to determine the association between clinical characteristics and COX-2 methylation in breast cancer patients.


METHODS
Using bisulfite modification and a methylation-specific PCR, we examined the methylation status of the COX-2 promoter in primary tumors from 110 breast cancer patients. Meanwhile, the expression of COX-2 protein was determined by immunohistochemistry (IHC).


RESULTS
Twenty out of 110 (18.2%) primary breast cancers showed aberrant methylation of the 5' region of COX-2. Loss of expression of COX-2 protein was found in all tumors with COX-2 methylation. Methylation of COX-2 was strongly correlated with tumor size (P = 0.026), presence of axillary lymph node metastasis (P = 0.001) and lymphovascular permeation (P = 0.034).


CONCLUSIONS
Our data suggest that COX-2 methylation is associated with good prognostic factors in breast cancer patients. COX-2 promoter methylation may be one of the mechanisms by which tumor cells regulate COX-2 expression.
Chow
L W C
LW
Hung Chao Hong Integrated Center for Breast Diseases, Department of Surgery, The University of Hong Kong Medical Center, China. lwcchow@hkucc.hku.hk
Zhu
L
L
Loo
W T Y
WT
Lui
E L H
EL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000201:enzymology*; D018899:CpG Islands / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D008745:Methylation; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004273:DNA, Neoplasm; D051546:Cyclooxygenase 2