[The effect of cyclooxygenase-2 on lymphangiogenesis in breast cancer].
OBJECTIVE
To study the effect of cyclooxygenase-2 (COX-2) on lymphangiogenesis in breast cancer.


METHODS
By the means of immunohistochemistry, COX-2, vascular endothelial growth factor-C (VEGF-C) and D2-40 were examined in the tissue samples of primary tumors from 94 patients underwent surgical resections for breast cancer from November 1998 to March 2002. Eighty-three patients were followed-up. The expressions of VEGF-C mRNA and protein were detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blot in MDA-MB-231 cell lines by the treatment of selective COX-2 inhibitor Nimesulide at different doses. The expressions of VEGF-C protein were evaluated in MDA-MB-231 cells treated by PGE2 (1 microg/ml) and Trastuzumab (1 microg/ml), respectively.


RESULTS
COX-2 over-expression was observed in 46.8% of surgical specimens (44/94), while VEGF-C overexpression occurred in 51.1% of tumor samples (48/94). COX-2 was strongly correlated with VEGF-C expression (P < 0.01), micro-lymphatic vessels (P = 0.032) and metastatic lymph nodes (P = 0. 035). Patients with COX-2 positive tumors had a significant shorter survival time than those with negative tumors did, including disease-free survival (P = 0.010) and overall survival (P = 0.040). Nimesulide could down-regulate the expressions of VEGF-C mRNA and protein in a does-dependent manner, while PGE2 could up-regulate the expressions. The expression of VEGF-C protein up-regulated by PGE2 treatment was decreased by Trastuzumab.


CONCLUSIONS
COX-2 over-expression can up-regulate the expression of VEGF-C. VEGF-C might promote lymph node metastasis by a lymph-angiogenic pathway, then affect the prognosis of the patients with breast cancer.
Guo
Gui-Long
GL
Department of Oncological Surgery, First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, China. guoguilong@sina.com.cn
Yang
Guang-Lun
GL
Li
Zhuo-Ying
ZY
You
Jie
J
Yang
Kai
K
Huang
Du-Ping
DP
Hu
Xiao-Qu
XQ
Zhang
Xiao-Hua
XH
D000293:Adolescent; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000378:metabolism / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011379:Prognosis; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics / Q000378:metabolism
D042582:Vascular Endothelial Growth Factor C; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human