PS2和组织蛋白酶D在710例人类原发性乳腺癌中的预后价值：多变量分析

Prognostic value of PS2 and cathepsin D in 710 human primary breast tumors: multivariate analysis.

作者信息

Foekens J A, van Putten W L, Portengen H, de Koning H Y, Thirion B, Alexieva-Figusch J, Klijn J G

机构信息

Department of Medical Oncology, Dr Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.

出版信息

J Clin Oncol. 1993 May;11(5):899-908. doi: 10.1200/JCO.1993.11.5.899.

DOI:10.1200/JCO.1993.11.5.899

PMID:8487052

Abstract

PURPOSE

Evaluation of the prognostic value of cytosolic PS2 (pS2 protein) and cathepsin D in a large series of breast cancer patients by multivariate analysis taking into account steroid receptors and conventional prognostic factors.

PATIENTS AND METHODS

Prognostic factors were analyzed in 710 primary breast cancers (median follow-up, 4 years). PS2 and cathepsin D were measured by radiometric immunoassays. Estrogen receptor (ER) and progesterone receptor (PgR) status were assessed by radioligand binding assays and multiple-point Scatchard analysis.

RESULTS

The best cutoff point for PS2 to discriminate between positive (61% of the tumors) and negative was 2 ng/mg protein (univariate P value in 5-year relapse-free survival = .003). For cathepsin D, no sensible cutoff point could be chosen, since there was a continuous association between the level of cathepsin D and relapse rate (P = .001). In Cox multivariate analysis, relapse rate decreased with age of premenopausal/perimenopausal patients and with PS2 or steroid receptor positivity, and increased with the size of the tumor, the number of positive lymph nodes, and increasing levels of cathepsin D. In analysis for overall survival, age of both premenopausal/perimenopausal and postmenopausal patients, tumor size, the number of positive lymph nodes, ER/PgR, and PS2 were all independently associated with the rate of death. The level of cathepsin D was positively correlated with the rate of death, but this trend was not statistically significant. Separate Cox multivariate analyses for relapse-free survival in subgroups of patients as defined by nodal status showed that the contribution of PS2 and cathepsin D was the strongest in the node-negative subgroup. Node-negative patients with tumors containing PS2 values < or = 2 ng/mg protein and cathepsin D values more than 70 pmol/mg protein experienced a 4.5-fold increase in relapse rate as compared with those with PS2 levels greater than 2 ng/mg protein and cathepsin D levels < or = 30 pmol/mg protein.

CONCLUSION

PS2 and cathepsin D are independent prognostic factors in primary breast cancer and lymph node-negative patients.

摘要

目的

通过多变量分析，综合考虑类固醇受体和传统预后因素，评估胞质PS2（pS2蛋白）和组织蛋白酶D在大量乳腺癌患者中的预后价值。

患者与方法

对710例原发性乳腺癌患者（中位随访时间4年）的预后因素进行分析。通过放射免疫分析法测定PS2和组织蛋白酶D。通过放射性配体结合试验和多点Scatchard分析评估雌激素受体（ER）和孕激素受体（PgR）状态。

结果

PS2区分阳性（占肿瘤的61%）和阴性的最佳临界值为2 ng/mg蛋白（5年无复发生存率的单变量P值 =.003）。对于组织蛋白酶D，无法选择合理的临界值，因为组织蛋白酶D水平与复发率之间存在连续关联（P =.001）。在Cox多变量分析中，绝经前/围绝经期患者年龄、PS2或类固醇受体阳性时复发率降低，而肿瘤大小、阳性淋巴结数量增加以及组织蛋白酶D水平升高时复发率增加。在总生存分析中，绝经前/围绝经期和绝经后患者的年龄、肿瘤大小、阳性淋巴结数量、ER/PgR和PS2均与死亡率独立相关。组织蛋白酶D水平与死亡率呈正相关，但这种趋势无统计学意义。根据淋巴结状态定义的患者亚组中无复发生存的单独Cox多变量分析表明，PS2和组织蛋白酶D在淋巴结阴性亚组中的作用最强。与PS2水平大于2 ng/mg蛋白且组织蛋白酶D水平≤30 pmol/mg蛋白的患者相比，PS2值≤2 ng/mg蛋白且组织蛋白酶D值大于70 pmol/mg蛋白的淋巴结阴性肿瘤患者复发率增加4.5倍。