ABSTRACT
PURPOSE: G-protein coupled estrogen receptor 1 (GPER) probably play important roles in the progression of breast cancer including endocrine therapeutic resistance. We evaluated GPER in primary breast cancers. METHODS: Immunohistochemistry was used to detect GPER in paraffin-embedded tissues of primary breast cancers from 423 patients and GPER expression was correlated with clinicopathological factors. RESULTS: GPER was expressed in 63.8% of specimens, coexpressed with estrogen receptor alpha (ERalpha) in 36.6% of tumors and was positive in 62.5% of the ERalpha-negative tumors. The expression of GPER had no relationship with the status of ERalpha, progesterone receptor and HER2. Although the expression of GPER was significantly inversely related with nodal status (p=0.045), no correlation between GPER expression and other clinicopathological variables (age, menstruation status, tumor size, stage, histologic grade, Nottingham Prognostic Index or pathological type) was found. CONCLUSION: GPER and ERalpha exhibited independent expression pattern of distribution in primary breast cancers. A long-term follow-up and a more definite molecular phenotype for ER are necessary in confirming studies.
Subject(s)
Female , Humans , Breast , Breast Neoplasms , Estrogen Receptor alpha , Estrogens , Follow-Up Studies , GTP-Binding Proteins , Immunohistochemistry , Menstruation , Phenotype , Receptors, ProgesteroneABSTRACT
<p><b>OBJECTIVE</b>To study the effect of cyclooxygenase-2 (COX-2) on lymphangiogenesis in breast cancer.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Middle Aged , Breast Neoplasms , Metabolism , Pathology , Cyclooxygenase 2 , Metabolism , Physiology , Follow-Up Studies , Lymphangiogenesis , Lymphatic Metastasis , Prognosis , Vascular Endothelial Growth Factor C , Genetics , MetabolismABSTRACT
Objective To investigated the expression of intracellular adhesion molecule-1 (ICAM-1)in mouse to rat cardiac xenograft and the effects of leflunomide and cyclosporine.Methods NIH mice and Wistar rats served as donors and recipients respectively.Mouse to rat heterotopic heart transplantation was performed(in the neck).The experiments were divided into 4 groups:CsA group,leflunomide(Lef)group,CsA+Lef group,control group.It was the time of rejection that no pulsation could be detected in the transplanted heart.The expression of ICAM-1 protein in cardiac xenograft tissue was detected by immunohistochemistry and Western blot in each group.Results The survival time of cardiac xenograft in control group,CsA group,Lef group and CsA+Lef group was (2.17?0.41),(2.50?1.05),(4.17?1.33)and(6.50?2.56)days respectively.The expression of ICAM-1 protein(IOD)in cardiac xenograft tissue in control group,CsA group,Lef group and CsA+ Lef group was 155.40?5.33,150.73?5.13,104.65?6.15 and 29.24?2.76 respectively.Conclu- sion The expression of ICAM-1 protein was strong in mouse to rat cardiac xenograft.The combined use of Lef and CsA can significantly suppress the expression of ICAM-1 protein in the cardiac xenograft.