Comparison of mitotic index, in vitro bromodeoxyuridine labeling, and MIB-1 assays to quantitate proliferation in breast cancer

Comparison of mitotic index, in vitro bromodeoxyuridine labeling, and MIB-1 assays to quantitate proliferation in breast cancer
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DOI:
10.1200/jco.1999.17.2.470
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发表时间:
1999-02-01
影响因子:
45.3
通讯作者:
Edgerton, SM
Edgerton, SM
中科院分区:
医学1区
文献类型:
--
作者:
Thor, AD;Liu, SQ;Edgerton, SM

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目的:探讨体外溴脱氧尿苷 (BrDu) 标记在预后价值方面可能优于 MIB-1 免疫染色的假设,因为它可以更选择性地标记 S 期细胞。方法:对 1988 年至 1993 年间手术切除的 486 名乳腺癌患者(59% 淋巴结阴性,41% 淋巴结阳性)(中位随访 62 个月)进行前瞻性细胞增殖评估。体外 BrDu 摄取测定、回顾性有丝分裂指数和 MIB-1 标记。结果:MIB-1、BrDu 标记和有丝分裂指数衍生的增殖数据高度相关。每一个都与大多数其他预后标志物类似地相关,尽管这些关系并不完全相同。通过单变量分析,淋巴结状态是所有患者最重要的预后变量。较高的 BrDu 标记指数、MIB-1 免疫标记和有丝分裂指数也与整个患者组以及淋巴结阴性患者的无病生存期 (DFS) 和疾病特异性生存期缩短相关。对于淋巴结阳性患者,细胞增殖和生存之间的关联要弱得多。多变量模型证实,淋巴结状态、肿瘤大小和增殖数据可预测所有患者以及淋巴结阴性患者的生存期,尽管 MIB-1 与有丝分裂指数或体外 BrDu 数据相比与结果的关系更为密切。对于 T1NOMO 疾病患者 (n = 172),DFS 的唯一显着预测因子是增殖率(有丝分裂指数或 MIB-1)和肿瘤分级。结论:增殖率可预测乳腺癌的复发和生存。这种效应在淋巴结阴性患者中更为明显。体外 BrDu 数据自然优于 MIB-1 和有丝分裂计数。 (C) 1999 年,美国临床肿瘤学会。
Purpose: To investigate the hypothesis that in vitro bromodeoxyuridine (BrDu) labeling might be superior to MIB-1 immunostaining for prognostic value, because it more selectively labels cells during the S phase.Methods: Four hundred eighty-six patients with breast cancers (59% lymph node-negative, 41% lymph node-positive) surgically excised between 1988 and 1993 (median follow-up, 62 months) were evaluated for cellular proliferation using prospective in vitro BrDu uptake assays, retrospective mitotic indices, and MIB-1 labeling.Results: MIB-1, BrDu labeling, and mitotic index-derived proliferation data were highly correlated. Each was similarly associated with most other markers of prognosis, although these relationships were not identical. By univariate analysis, nodal status was the most significant prognostic variable for all patients. Higher BrDu labeling index, MIB-1 immunolabeling, and mitotic index were also associated with shortened disease-free survival (DFS) and disease-specific survival for the entire patient group, as well as for node-negative patients. The association between cellular proliferation and survival was much weaker for node-positive patients. Multivariate models confirmed that nodal status, tumor size, and proliferation data predicted survival in all patients as well as those with node-negative disease, although MIB-1 was somewhat more closely associated with outcome than mitotic index or in vitro BrDu data. For patients with T1NOMO disease (n = 172), the only significant predictors of DFS were proliferation rate (mitotic index or MIB-1) and tumor grade.Conclusions: Proliferation rate predicts recurrence and survival in breast cancer. This effect is more pronounced in node-negative patients. In vitro BrDu data are nat superior to MIB-1 and mitotic counting. (C) 1999 by American Society of Clinical Oncology.