Assessment of proliferative activity in breast cancer: MIB-1 immunohistochemistry versus mitotic figure count

Assessment of proliferative activity in breast cancer: MIB-1 immunohistochemistry versus mitotic figure count
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DOI:
10.1016/s0046-8177(99)90062-x
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发表时间:
1999-11-01
期刊:
影响因子:
3.3
通讯作者:
Gown, AM
Gown, AM
中科院分区:
医学3区
文献类型:
--
作者:
Lehr, HA;Hansen, DA;Gown, AM

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增殖活性是乳腺癌诊断中最重要的单一预后参数之一,并且增殖活性的历史悠久的测量,有丝分裂像计数,是大多数组合预后评分的组成部分。细胞周期特异性抗原Ki-67的检测和抗Ki-67抗体的开发,包括石蜡反应性抗体MIB-1,已经建立了细胞周期特异性抗原的免疫组织化学检测作为乳腺癌诊断中增殖活性的测量。本研究旨在将有丝分裂相计数与。通过MIB-1免疫组织化学评估增殖活性,考虑到5位病理学家在估计有丝分裂像计数方面的观察者间可靠性。在32例连续浸润性导管乳腺癌中,核分裂像计数由5名病理学家独立进行。有丝分裂活性表示为每10个高倍视野的有丝分裂像数,并根据Scarff Bloom Richardson系统进行3级评分。使用MIB-1抗体、热诱导表位修复和标准抗生物素蛋白-生物素-免疫过氧化物酶法进行免疫组织化学。通过半定量估计(阳性肿瘤细胞%)和图像分析(MIB-1阳性细胞数/mm(2)),在3个代表性20 X视野中评估MIB-1免疫组织化学。我们发现4位经验丰富的病理学家在每10个高倍视野的核分裂像和3级评分系统中观察者之间存在高度相关性。我们观察到半定量和定量MIB-1免疫组化与每10个高倍视野的有丝分裂像数量之间存在显著相关性(尽管相关性较弱)(r在0.36和0.53之间),但当有丝分裂活性在3级评分系统中表达时,5名观察者中有3名观察者失去了这种显著性。本研究证实,在有经验的病理学家手中,有丝分裂像计数是一种有效的、可重复的方法,可用于评估乳腺癌常规诊断中的增殖活性。与MIB-1免疫组化的统计学显著相关性(尽管仅为弱相关性)与其他人获得的结果一致,并表明MIB-1免疫组化不能通过简单的转换因子转化为组合预后评分以取代历史悠久的有丝分裂像计数。版权所有(C)1999 W.B.桑德斯公司
The proliferative activity is one of the most important single prognostic parameters in breast cancer diagnosis and the time-honored measure of proliferative activity, the mitotic figure count, is an integral component of most combined prognostic scores. The detection of the cell cycle-specific antigens Ki-67, and the develop ment of anti-Ki-67 antibodies, including the paraffin-reactive antibody MIB-1, have established immunohistochemical detection of cell cycle-specific antigens as a measure of proliferative activity in breast cancer diagnosis. The current study was performed to correlate mitotic figure counts with. the proliferative activity as assessed by MIB-1 immunohistochemistry, taking into consideration the interobserver reliability of 5 pathologists in estimating mitotic figure counts. In 32 consecutive invasive ductal breast carcinomas, mitotic figure counts were performed independently by 5 pathologists. Mitotic activity was expressed as number of mitotic figures per 10 high-power fields and in a 3-tier score according to the Scarff Bloom Richardson system. Immunohistochemistry was performed using MIB-1 antibody, heat-induced epitope retrieval, and the standard avidin-biotin-immunoperoxidase method. MIB-1 immunohistochemistry was assessed in 3 representative 20X fields by semiquantitative estimation (% of tumor cells positive) and by image analysis (number of MIB-1-positive cells/mm(2)). We found a high degree of interobserver correlation among 4 experienced pathologists, in both mitotic figures per 10 high-power fields and the 3-tier scoring system. We observed significant, albeit weak, correlations between semiquantitative and quantitative MIB-1 immunohistochemistry and the number of mitotic figures per 10 high-power fields (r between .36 and .53), but this significance was lost in 3 of the 5 observers when mitotic activity was expressed in the 3-tier scoring system. This study confirms mitotic figure counting in the hands of experienced pathologists as a valid, reproducible means of assessing proliferative activity in routine breast cancer diagnosis. The statistically significant, albeit only weak, correlation with MIB-1 immunohistochemistry is in agreement with results obtained by others and suggests that MIB-1 immunohistochemistry cannot be translated by a simple conversion factor into combined prognostic scores to replace the time-honored mitotic figure counts. Copyright (C) 1999 by W.B. Saunders Company.