A PROSPECTIVE-STUDY OF THE PROGNOSTIC VALUE OF CATHEPSIN-D LEVELS IN BREAST-CANCER CYTOSOL
A PROSPECTIVE-STUDY OF THE PROGNOSTIC VALUE OF CATHEPSIN-D LEVELS IN BREAST-CANCER CYTOSOL
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DOI：
10.1002/1097-0142(19930315)71:6
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发表时间：
1993-03-15
期刊：
影响因子：
6.2
通讯作者：
ROCHEFORT, H
中科院分区：
文献类型：
--
作者：
PUJOL, P;MAUDELONDE, T;ROCHEFORT, H
背景组织蛋白酶D是一种在大多数乳腺癌细胞中过度表达和异常分泌的溶酶体蛋白酶。几项回顾性临床研究表明，组织蛋白酶D是乳腺癌的独立预后因子，与较高的复发风险和较短的总生存期相关。据作者所知，这是第一个前瞻性研究，其中组织蛋白酶D的预后价值进行了研究，在123例原发性乳腺癌谁是5年的1985年3月至1990年12月之间。乳腺癌细胞质中的组织蛋白酶D浓度测定使用固相夹心免疫酶法。采用考克斯比例风险法进行多因素分析，确定最重要的预后因素。组织蛋白酶D的中位值为20.8 pmol/mg蛋白质，约为使用市售试剂盒进行的后续测定中发现的中位值的一半，并在大多数回顾性研究中报告。组织蛋白酶D状态或水平仅与腋窝淋巴结受累相关。单因素分析显示，高水平的组织蛋白酶D（> 20 pmol/mg蛋白）与较高的复发风险和较短的总生存期相关（分别为P < 0.01和P < 0.03）。多因素分析显示，组织蛋白酶D水平升高、孕激素受体阴性和淋巴结转移是预测无复发生存率的最重要因素（分别为P = 0.02、P < 0.01和P < 0.05）。组织蛋白酶D水平对淋巴结阳性患者有预后价值（P = 0.001），并且通过分离高危亚组患者（组织蛋白酶D水平高;孕酮受体状态阴性），其与孕酮受体状态的相关性似乎特别有用。这是第一项前瞻性研究，证实了组织蛋白酶D水平与其他主要预后因素相关的预后价值。下一步将是确定组织蛋白酶D水平高的患者是否会从辅助治疗中获益。
Background. Cathepsin D is a lysosomal protease overexpressed and abnormally secreted in most breast cancer cells. Several retrospective clinical studies have shown that cathepsin D is an independent prognostic factor in breast cancer that is associated with a higher risk of recurrence and a shorter overall survival.Methods. To the authors' knowledge, this is the first prospective study in which the prognostic value of cathepsin D was studied in 123 patients with primary breast cancer who were followed for 5 years between March 1985 and December 1990. Cathepsin D concentrations in breast cancer cytosol were measured using a solid-phase sandwich immunoenzymatic assay. The most significant prognostic factors were identified by multivariate analysis using the Cox proportional-hazards method.Results. The median value of cathepsin D was 20.8 pmol/mg of protein, which was approximately half than the median value found in subsequent assays done using a commercially available kit and reported in most retrospective studies. The cathepsin D status or level was correlated only with axillary lymph node involvement. A univariate analysis showed that high levels of cathepsin D (> 20 pmol/mg of protein) were correlated with a higher risk of recurrence and a shorter overall survival (P < 0.01 and P < 0.03, respectively). Using multivariate analysis, a high cathepsin D level, a negative progesterone receptor status, and lymph node involvement were the most important factors for predicting relapse-free survival (P = 0.02, P < 0.01, and P < 0.05, respectively). The cathepsin D level had prognostic value in patients with node-positive disease (P = 0.001) and appeared to be particularly useful in association with the progesterone receptor status by isolating a high-risk subgroup of patients (high cathepsin D level; negative progesterone receptor status).Conclusions. This first prospective study confirmed the prognostic value of the cathepsin D level in association with other major prognostic factors. The next step will be to determine whether the subset of patients with high cathepsin D levels would benefit from adjuvant therapy.