Correlation between cyclooxygenase-2 expression and angiogenesis in human breast cancer.
OBJECTIVE
Cyclooxygenase (COX)-2 is overexpressed in breast cancer and may have a role in regulating tumor growth via effects on angiogenesis, cell proliferation, or apoptosis. This study aimed to derive data from human breast carcinomas to help substantiate or refute these relationships.


METHODS
We performed immunohistochemical analysis of a set of 86 breast tumors for COX-2, estrogen receptor (ER), progesterone receptor (PGR), HER-2, Ki67 (a marker of proliferation), and CD31 (an endothelial cell marker of angiogenesis).


RESULTS
COX-2 protein expression was detected in 79% of all tumors studied, ER was detected in 79% of all tumors studied, PGR was detected in 73% of all tumors studied, and HER-2 was detected in 16% of all tumors studied. COX-2 protein expression did not significantly correlate with tumor size, grade, axillary lymph node status, or the presence of vascular invasion. A significant negative correlation (P < 0.001) was observed between ER and Ki67. COX-2 expression showed a significant linear correlation with CD31 staining (P < 0.001). No significant correlations were observed between COX-2 and ER, PGR, or HER-2.


CONCLUSIONS
This study demonstrates a novel relationship between COX-2 expression and the neovasculature of human breast adenocarcinomas. If this is a functional relationship, it provides support for a potential therapeutic role of COX-2 inhibitors in human breast cancer tissue via their antiangiogenic properties.
Davies
Giles
G
Academic Departments of Biochemistry, Royal Marsden Hospital, London SW3 6JJ, United Kingdom. mitch@icr.ac.uk
Salter
Janine
J
Hills
Margaret
M
Martin
Lesley-Ann
LA
Sacks
Nigel
N
Dowsett
Mitch
M
D000328:Adult; D000368:Aged; D017209:Apoptosis; D001943:Breast Neoplasms / Q000201:enzymology*; D002455:Cell Division; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007527:Isoenzymes / Q000096:biosynthesis*; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008207:Lymphatic Metastasis; D008565:Membrane Proteins; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis
D051546:Cyclooxygenase 2; D007527:Isoenzymes; D019394:Ki-67 Antigen; D008565:Membrane Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011451:Prostaglandin-Endoperoxide Synthases; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C496540:PTGS2 protein, human