RESUMO
BACKGROUND: Vascular endothelial growth factor-C (VEGF-C) is the main inducer of lymphangiogenesis. VEGF-C overexpression is associated with lymphovascular tumor cell invasion, an increased rate of lymph node metastasis and adverse prognosis in various human cancers. However, little is known about the upstream inducers of VEGF-C expression. Recent studies have shown that human epidermal growth factor receptor 2 (HER2/neu) overexpression is associated with high VEGF-C levels in human breast cancer cells. In addition to blocking of HER2/neu, tyrosine kinase significantly decreased VEGF-C expression in vitro. PATIENTS AND METHODS: VEGF-C expression, lymphatic microvessel density (LMVD), lymphovascular invasion (LVI) and HER2/neu expression were evaluated with immunohistochemical/FISH methods in a collective of 150 lymph node-positive human breast cancers with long-term follow-up. RESULTS: Cases with 3+ HER2/neu protein expression showed a significantly stronger VEGF-C expression than all others cases (P = 0.006). In addition, we found a significant correlation between VEGF-C expression and LMVD (P = 0.012) and a strong positive association between LMVD and LVI (P < 0.001). CONCLUSION: Our data provide evidence for a clinically relevant association between HER2/neu and VEGF-C expression in human breast cancer. Inhibiting HER2/neu may reduce tumor progression by blocking VEGF-C-mediated tumor cell proliferation and lymphogenic metastasis.
Assuntos
Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Carcinoma Lobular/metabolismo , Linfonodos/patologia , Linfangiogênese , Receptor ErbB-2/metabolismo , Fator C de Crescimento do Endotélio Vascular/metabolismo , Adulto , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/patologia , Carcinoma Lobular/terapia , Estudos de Coortes , Feminino , Seguimentos , Amplificação de Genes , Humanos , Técnicas Imunoenzimáticas , Hibridização in Situ Fluorescente , Linfonodos/metabolismo , Metástase Linfática , Vasos Linfáticos/metabolismo , Vasos Linfáticos/patologia , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Estudos Prospectivos , Receptor ErbB-2/genética , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Taxa de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: Retrospective analysis of the results of rt-PA thrombolysis in the treatment of acute thromboembolic occlusion of the upper limb. METHODS: Of 55 patients with demonstrated acute embolic arterial occlusion, rt-PA thrombolysis was performed on 40 occlusions in 38 patients (23 women with a mean age of 62 years, range 32-85 years; 15 men with a mean age of 65 years, range 32-92 years) according to the following design: 6 mg rt-PA/hr for 30 min, 3 mg rt-PA/hr for the next 30 min, 1 mg rt-PA/hr for 7 hr, and 0.4 mg rt-PA/hr until the end of lysis. Onset of symptoms varied from 1 to 14 days. Included were three isolated upper-arm occlusions, nine combined brachial and forearm occlusions, and 28 forearm and hand artery occlusions. RESULTS: The overall success rate was 55%. The lysis results for isolated upper arm, combined brachial and forearm occlusions, and forearm and hand artery occlusions were 100%, 66%, and 46%, respectively. In eight patients surgical embolectomy had to be performed after failed thrombolysis. No amputation was required in the follow-up period. No lethal complications occurred. CONCLUSIONS: Interventional rt-PA treatment of proximal upper-extremity arterial occlusions may be performed with comparable success rates to surgical embolectomy and without severe complications. For distal occlusions the results are inferior to the success rates obtained with surgery.