Cyclooxygenase-2 (COX-2) has an important role in the promotion of
carcinogenesis,
tumor invasion and angiogenesis.
Vascular endothelial growth factor (
VEGF) is a proangiogenic factor that is up-regulated in various
tumors.
VEGF has been shown to interact with COX-derived
prostaglandins in angiogenesis. Cyclin D1 gene overexpression and amplification have been shown to play a role as prognostic factors in many human
cancers. To better understand the roles of these genes in mammary
carcinoma, the immunohistochemical expression patterns of COX-2 and
VEGF were evaluated in relationship with
cyclin D1 overexpression,
tumor stage, clinicopathologic parameters and patient survival in 128 mammary infiltrating duct
carcinomas. The expressions of COX-2/
VEGF, COX-2/
cyclin D1, and
VEGF/
cyclin D1 were evaluated using double immunofluorescein staining with a confocal scanning
laser microscope. A positive expression was seen in 41% for COX-2, 47% for
VEGF, and 66% for
cyclin D1 in the cases with
breast cancer. There was correlation in positive expression of COX-2 or
VEGF with histologic grade,
lymph node metastasis, and
tumor size. Conversely, a significant inverse relation was observed between
VEGF and patient age. There was a correlation in overexpression of
cyclin D1 with
lymph node metastasis, survival rate and survival length. Significant correlations were observed between COX-2 and
VEGF as well as COX-2 and
cyclin D1. Co-expression of only COX-2 and
VEGF was detected with significance. These results indicate that elevated COX-2 or
VEGF expression or
cyclin D1 overexpression is more common in
breast cancer patients with poor prognostic characteristics and is partly associated with an unfavorable outcome. The present findings support the efforts to initiate clinical trials on the efficacy of
COX-2 inhibitors in adjuvant treatment of
breast cancer.