Ben-Izhak Ofer, Kaplan-Cohen Victoria, Ilan Neta, Gan Shlomit, Vlodavsky Israel, Nagler Rafael
Department of Pathology, Rambam Medical Center, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Neoplasia. 2006 Oct;8(10):879-84. doi: 10.1593/neo.06382.
Upregulation of the endo-beta-D-glucuronidase, heparanase, was noted in an increasing number of human malignancies. Heparanase expression correlated with enhanced local and distant metastatic spread, increased vascular density, and reduced postoperative survival.
We analyzed heparanase expression in 60 patients (aged 59 +/- 17 years) with malignant salivary tumors (39 males and 21 females) using immunohistochemistry. We applied antiheparanase antibody 733, which has previously been shown to preferentially recognize a 50-kDa active heparanase subunit over a 65-kDa latent enzyme. Thus, immunostaining can directly be correlated with enzymatic activity.
Heparanase staining was positive (> 0) in 70% of tumors (42 of 60 patients) and was negative (0) in the remaining 30% (18 patients). The cumulative survival of patients diagnosed as heparanase-negative (n = 18) at 300 months was 70% (95% confidence interval = 35-88). In contrast, the cumulative survival of patients diagnosed as heparanase-positive (n = 42) at 300 months was 0% (statistically significant difference, P = .035).
Heparanase expression levels inversely correlate with the survival rates of salivary gland cancer patients, clearly indicating that heparanase is a reliable prognostic factor for this malignancy and an attractive target for anticancer drug development.
在越来越多的人类恶性肿瘤中，发现内-β-D-葡萄糖醛酸酶（乙酰肝素酶）上调。乙酰肝素酶的表达与局部和远处转移扩散增强、血管密度增加及术后生存率降低相关。
我们采用免疫组织化学方法分析了60例（年龄59±17岁）恶性唾液腺肿瘤患者（男性39例，女性21例）的乙酰肝素酶表达情况。我们使用了抗乙酰肝素酶抗体733，该抗体先前已被证明优先识别50 kDa的活性乙酰肝素酶亚基而非65 kDa的潜在酶。因此，免疫染色可直接与酶活性相关联。
70%的肿瘤（60例患者中的42例）乙酰肝素酶染色呈阳性（>0），其余30%（18例患者）呈阴性（0）。诊断为乙酰肝素酶阴性（n = 18）的患者在300个月时的累积生存率为70%（95%置信区间 = 35 - 88）。相比之下，诊断为乙酰肝素酶阳性（n = 42）的患者在300个月时的累积生存率为0%（差异有统计学意义，P = .035）。
乙酰肝素酶表达水平与唾液腺癌患者的生存率呈负相关，清楚地表明乙酰肝素酶是这种恶性肿瘤的可靠预后因素，也是抗癌药物开发的一个有吸引力的靶点。
