Pujol P, Maudelonde T, Daures J P, Rouanet P, Brouillet J P, Pujol H, Rochefort H
INSERM U 148, Montpellier, France.
Cancer. 1993 Mar 15;71(6):2006-12. doi: 10.1002/1097-0142(19930315)71:6<2006::aid-cncr2820710614>3.0.co;2-q.
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.
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.
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).
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.
组织蛋白酶D是一种溶酶体蛋白酶，在大多数乳腺癌细胞中过表达且异常分泌。多项回顾性临床研究表明，组织蛋白酶D是乳腺癌的一个独立预后因素，与更高的复发风险和更短的总生存期相关。
据作者所知，这是第一项前瞻性研究，对1985年3月至1990年12月期间随访5年的123例原发性乳腺癌患者的组织蛋白酶D的预后价值进行了研究。采用固相夹心免疫酶法测定乳腺癌细胞溶质中组织蛋白酶D的浓度。使用Cox比例风险法通过多变量分析确定最显著的预后因素。
组织蛋白酶D的中位数为20.8 pmol/mg蛋白质，约为随后使用市售试剂盒进行检测并在大多数回顾性研究中报道的中位数的一半。组织蛋白酶D状态或水平仅与腋窝淋巴结受累相关。单变量分析显示，组织蛋白酶D水平高（>20 pmol/mg蛋白质）与更高的复发风险和更短的总生存期相关（分别为P<0.01和P<0.03）。使用多变量分析，组织蛋白酶D水平高、孕激素受体状态为阴性和淋巴结受累是预测无复发生存期的最重要因素（分别为P = 0.02、P<0.01和P<0.05）。组织蛋白酶D水平在淋巴结阳性疾病患者中具有预后价值（P = 0.001），并且通过分离出高危患者亚组（组织蛋白酶D水平高；孕激素受体状态为阴性），似乎在与孕激素受体状态相关时特别有用。
这项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水平高的患者亚组是否能从辅助治疗中获益。
