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头颈部鳞状细胞癌中肝素酶的表达与增殖减少和生存改善相关。

Heparanase expression in head and neck squamous cell carcinomas is associated with reduced proliferation and improved survival.

机构信息

Institute of Pathology, University of Heidelberg, Heidelberg, Germany.

出版信息

Histopathology. 2011 May;58(6):944-52. doi: 10.1111/j.1365-2559.2011.03834.x.

DOI:10.1111/j.1365-2559.2011.03834.x
PMID:21585429
Abstract

AIMS

Cellular expression of heparanase, a degrading enzyme of the extracellular matrix, is associated with poorer prognosis in several cancers. The present analysis, has studied the role of heparanase in tumour growth and clinical outcome in patients with head and neck squamous cell carcinoma (HNSCC).

METHODS AND RESULTS

We analysed the cellular expression of the active form of heparanase in 71 human HNSCCs, using immunohistochemistry. The results were compared with clinicopathological data and, in 65 cases with immunoreactivity for the proliferation marker, MIB1. Cellular heparanase expression was detected in 41 of 71 (57.74%) cases; in particular, UICC IV-stage tumours showed high heparanase levels. Heparanase was localized mainly in the cytoplasm and, to a lesser extent, at the cell membrane. High levels of heparanase were significantly correlated with an almost four-fold decrease in MIB1 labelling (P = 0.006). Comparison with clinical outcome by multivariate analysis revealed that patients with high-level heparanase expression had prolonged overall survival (P = 0.029).

CONCLUSIONS

Although heparanase was mainly found in late-stage HNSCCs, cellular heparanase expression in HNSCCs was associated with prolonged overall survival. We propose that the proliferation-reducing effect of high heparanase levels might outweigh the tumour-promoting effects of heparanase, especially in advanced tumours.

摘要

目的

细胞分泌的乙酰肝素酶是细胞外基质的降解酶,其在多种癌症中与预后不良有关。本分析研究了乙酰肝素酶在头颈部鳞状细胞癌(HNSCC)患者肿瘤生长和临床结局中的作用。

方法和结果

我们使用免疫组织化学分析了 71 例人 HNSCC 中乙酰肝素酶的活性形式的细胞表达。将结果与临床病理数据进行了比较,并在 65 例具有增殖标志物 MIB1 免疫反应性的病例中进行了比较。在 71 例病例中的 41 例(57.74%)中检测到细胞乙酰肝素酶表达;特别是 UICC IV 期肿瘤显示高水平的乙酰肝素酶。乙酰肝素酶主要定位于细胞质,在一定程度上也定位于细胞膜。高水平的乙酰肝素酶与 MIB1 标记的近四倍下降显著相关(P=0.006)。通过多变量分析与临床结局进行比较显示,高水平乙酰肝素酶表达的患者总生存期延长(P=0.029)。

结论

尽管乙酰肝素酶主要存在于晚期 HNSCC 中,但 HNSCC 中的细胞乙酰肝素酶表达与总生存期延长相关。我们提出,高水平乙酰肝素酶的增殖减少作用可能超过乙酰肝素酶的促肿瘤作用,尤其是在晚期肿瘤中。

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