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舌癌中乙酰肝素酶的上调:组织和唾液分析

Heparanase up-regulation in tongue cancer: tissue and saliva analysis.

作者信息

Nagler Rafael, Ben-Izhak Ofer, Cohen-Kaplan Victoria, Shafat Itay, Vlodavsky Israel, Akrish Sharon, Ilan Neta

机构信息

Department of Oral and Maxillofacial Surgery and Oral Biochemistry Laboratory, Rambam Medical Center and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.

出版信息

Cancer. 2007 Dec 15;110(12):2732-9. doi: 10.1002/cncr.23095.

Abstract

BACKGROUND

Heparanase up-regulation has been correlated with reduced postoperative survival in various cancers.

METHODS

Heparanase expression was analyzed in 60 consenting tongue (mobile) cancer patients by means of immunohistochemistry. Heparanase levels were also analyzed in the saliva of both healthy controls and tongue cancer patients using a novel heparanase enzyme-linked immunosorbent assay method.

RESULTS

Heparanase staining was positive (>0) in 92% and negative (=0) in 8% of the tumors and staining intensity correlated with tumor size and tumor stage. Moreover, the survival probability of patients negative for heparanase (=0) at 60 months was 100%, compared with only 41% for patients positive for heparanase (>0), suggesting that heparanase may serve as a prognostic factor for this malignancy and an attractive target for anticancer drug development. Heparanase was detected in the saliva of healthy controls and the mean concentration was determined as 119 +/- 37 pg/mL. Importantly, a nearly 3-fold increase of heparanase levels was detected in saliva collected from tongue cancer patients (334 +/- 69 pg/mL), a difference that is statistically highly significant (P = .004).

CONCLUSIONS

These findings support heparanase up-regulation in tongue cancer and raise the possibility of using this simple test as a diagnostic tool to monitor tongue cancer progression and response to treatment.

摘要

背景

在多种癌症中,硫酸乙酰肝素酶上调与术后生存率降低相关。

方法

通过免疫组织化学分析60例同意参与的舌(活动部)癌患者的硫酸乙酰肝素酶表达。还使用一种新型硫酸乙酰肝素酶酶联免疫吸附测定方法分析了健康对照者和舌癌患者唾液中的硫酸乙酰肝素酶水平。

结果

92%的肿瘤硫酸乙酰肝素酶染色呈阳性(>0),8%呈阴性(=0),染色强度与肿瘤大小和肿瘤分期相关。此外,硫酸乙酰肝素酶阴性(=0)的患者60个月时的生存概率为100%,而硫酸乙酰肝素酶阳性(>0)的患者仅为41%,这表明硫酸乙酰肝素酶可能是这种恶性肿瘤的一个预后因素,也是抗癌药物开发的一个有吸引力的靶点。在健康对照者的唾液中检测到了硫酸乙酰肝素酶,平均浓度测定为119±37 pg/mL。重要的是,从舌癌患者收集的唾液中检测到硫酸乙酰肝素酶水平几乎增加了3倍(334±69 pg/mL),这一差异具有高度统计学意义(P = 0.004)。

结论

这些发现支持舌癌中硫酸乙酰肝素酶上调,并增加了将这种简单检测用作监测舌癌进展和治疗反应的诊断工具的可能性。

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