Department of Histopathology, Russell's Hall Hospital, Dudley, United Kingdom.
Aston Research Centre for Healthy Ageing and School of Life and Health Sciences, Aston University, Birmingham, United Kingdom.
Anticancer Res. 2014 Jun;34(6):2797-800.
BACKGROUND/AIM: Heparanase (HPA) contributes to breast cancer metastasis by facilitating the breakdown of the basement membrane and extracellular matrix. High expression of HPA is thought to be associated with increased nodal involvement and poor survival in patients with breast cancer. Overexpression of cyclooxygenase-2 (COX-2) in breast cancer is associated with indicators of poor prognosis such as lymph node metastasis, poor differentiation, and large tumor size. The underlying mechanism by which HPA and COX-2 overexpression increases the metastatic potential of breast cancer is not fully-understood. To enhance our understanding over these mechanisms, we aimed to investigate the relationship between the size of the tumor and HPA expression, tumor grade as well as lymph node status in patients with breast cancer.
Immunohistochemical analysis of HPA and COX-2 expression was performed on 246 breast tumor samples. The expression of HPA was correlated with COX-2 expression, tumor grade, lymph node status, oestrogen receptor status.
The overexpression of HPA and COX-2 was associated with increased likelihood of lymph node positivity in large, high-grade tumors. High-grade tumors with size greater than 20 mm, that overexpressed HPA, were 4-times more likely to be associated with lymph node involvement (OR 4.71, CI 1.21-18.25). Whereas, tumors greater than 20 mm in size were 5-times more likely to metastasize to the regional lymph nodes, if associated with overexpression of COX-2 (OR 5.5, CI 1.2-24.8).
Expression of HPA appears to be a key mechanism by which large, high-grade breast tumors metastasize to regional lymph nodes, while COX-2 overexpression may be an independent predictor of lymph node positivity.
背景/目的：肝素酶（HPA）通过促进基底膜和细胞外基质的分解，促进乳腺癌转移。HPA 的高表达被认为与乳腺癌患者淋巴结受累增加和生存率降低有关。乳腺癌中环氧化酶-2（COX-2）的过表达与淋巴结转移、低分化和肿瘤体积大等不良预后指标有关。HPA 和 COX-2 过表达增加乳腺癌转移潜能的潜在机制尚未完全阐明。为了更深入地了解这些机制，我们旨在研究乳腺癌患者肿瘤大小与 HPA 表达、肿瘤分级以及淋巴结状态之间的关系。
对 246 例乳腺癌肿瘤样本进行 HPA 和 COX-2 表达的免疫组织化学分析。分析 HPA 的表达与 COX-2 表达、肿瘤分级、淋巴结状态、雌激素受体状态的相关性。
HPA 和 COX-2 的过表达与大、高级别肿瘤中淋巴结阳性的可能性增加相关。HPA 过表达的高级别、大于 20mm 的大肿瘤发生淋巴结受累的可能性增加 4 倍（OR 4.71，CI 1.21-18.25）。而，大小大于 20mm 的肿瘤如果与 COX-2 的过表达相关，则更有可能转移到局部淋巴结（OR 5.5，CI 1.2-24.8）。
HPA 的表达似乎是大、高级别乳腺癌转移到局部淋巴结的关键机制，而 COX-2 的过表达可能是淋巴结阳性的独立预测因子。
