ST BORTOLO REG MED CTR,DEPT ONCOL,I-36100 VICENZA,ITALY. UNIV MILAN,NATL CANC INST,INST MED STAT & BIOMETRY,MILAN,ITALY.
Int J Oncol. 1994 Sep;5(3):559-64. doi: 10.3892/ijo.5.3.559.
Cathepsin D is a lysosomal aspartyl protease which seems to be involved in invasiveness and metastasis in breast carcinoma. Cathepsin D expression detected by immunocytochemistry is a new potentially useful prognostic marker. Additional research is warranted because: (i) few immunocytochemical studies have been performed to correlate cathepsin D expression and prognosis; (ii) a consensus has not yet been achieved on methodology and quality control issues; (iii) the association between cathepsin D expression and other new biological markers is poorly known and (iv) few studies have assessed whether cathepsin D expression is an independent prognostic marker when compared with other biological and clinico-pathological features using multivariate analysis. This study was undertaken in the same series of 165 stage I-II breast cancer patients (median follow-up of 5 years) already reported (Int J Oncol 4: 155-162, 1994) in whom cathepsin D was assessed using the D7E3 monoclonal antibody by immunocytochemistry in frozen specimens, using a standard peroxidase-antiperoxidase complex method. Cathepsin D was compared with another 7 biological markers, as well as with the conventional clinico-pathological features. Forty-two carcinomas of the 165 analyzed (25.5%) were cathepsin D-positive. This marker was significantly associated with c-erbB-2 expression (p=0.004) and tumour vascularization (p=0.02). Yet, a weak association was observed between cathepsin D and S-phase fraction (p=0.06). In univariate analysis cathepsin D was significantly associated both with relapse-free survival (p<0.01) and overall survival (p=0.02). In multivariate analysis, for relapse-free survival the variables cathepsin D/tumour vascularization, as well as S-phase fraction and EGFR, were significant and independent. For overall survival the variables cathepsin D/c-erbB-2 protein, as well as tumour vascularization and S-phase fraction were significant and independent. Immunocytochemical determination of cathepsin D, using the D7E3 antibody, seems to be a useful prognostic tool in early-stage breast cancer. In particular, cathepsin D adds prognostic information to tumour vascularization (in predicting relapse-free survival) and to c-erbB-2 expression (in predicting overall survival).
组织蛋白酶 D 是一种溶酶体天冬氨酸蛋白酶，似乎参与乳腺癌的侵袭和转移。免疫细胞化学检测到的组织蛋白酶 D 表达是一种新的潜在有用的预后标志物。需要进一步研究，因为：(i) 很少有免疫细胞化学研究来关联组织蛋白酶 D 表达和预后；(ii) 关于方法学和质量控制问题尚未达成共识；(iii) 组织蛋白酶 D 表达与其他新的生物学标志物之间的关联知之甚少；(iv) 很少有研究评估当使用多变量分析与其他生物学和临床病理特征进行比较时，组织蛋白酶 D 表达是否是独立的预后标志物。这项研究是在同一组 165 例 I-II 期乳腺癌患者（中位随访 5 年）中进行的，这些患者已经在先前的研究中报道过（Int J Oncol 4: 155-162, 1994），在这些患者中，使用 D7E3 单克隆抗体通过免疫细胞化学在冷冻标本中评估组织蛋白酶 D，使用标准过氧化物酶-抗过氧化物酶复合物方法。将组织蛋白酶 D 与其他 7 种生物学标志物以及常规临床病理特征进行比较。在分析的 165 例癌中，有 42 例为组织蛋白酶 D 阳性（25.5%）。该标志物与 c-erbB-2 表达（p=0.004）和肿瘤血管生成（p=0.02）显著相关。然而，在组织蛋白酶 D 与 S 期分数之间观察到弱相关性（p=0.06）。在单变量分析中，组织蛋白酶 D 与无复发生存率（p<0.01）和总生存率（p=0.02）显著相关。在多变量分析中，对于无复发生存率，组织蛋白酶 D/肿瘤血管生成以及 S 期分数和 EGFR 是显著和独立的。对于总生存率，组织蛋白酶 D/c-erbB-2 蛋白、肿瘤血管生成和 S 期分数是显著和独立的。使用 D7E3 抗体的组织蛋白酶 D 免疫细胞化学测定似乎是早期乳腺癌的一种有用的预后工具。特别是，组织蛋白酶 D 增加了肿瘤血管生成（预测无复发生存率）和 c-erbB-2 表达（预测总生存率）的预后信息。
