Ács Balázs, Kulka Janina, Kovács Kristóf Attila, Teleki Ivett, Tőkés Anna-Mária, Meczker Ágnes, Győrffy Balázs, Madaras Lilla, Krenács Tibor, Szász Attila Marcell
2nd Department of Pathology, Semmelweis University, Budapest 1091, Hungary.
1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest 1085, Hungary.
Hum Pathol. 2017 Jul;65:31-40. doi: 10.1016/j.humpath.2017.01.011. Epub 2017 Feb 8.
Although several antibodies are available for immunohistochemical detection of Ki-67, even the most commonly used MIB-1 has not been validated yet. Our aim was to compare 5 commercially available antibodies for detection of Ki-67 in terms of agreement and their ability in predicting prognosis of breast cancer. Tissue microarrays were constructed from 378 breast cancer patients' representative formalin-fixed, paraffin-embedded tumor blocks. Five antibodies were used to detect Ki-67 expression: MIB-1 using chromogenic detection and immunofluorescent-labeled MIB-1, SP-6, 30-9, poly, and B56. Semiquantitative assessment was performed by 2 pathologists independently on digitized slides. To compare the 5 antibodies, intraclass correlation and concordance correlation coefficient were used. All the antibodies but immunofluorescent-labeled MIB-1 (at 20% and 30% thresholds, P=.993 and P=.342, respectively) and B56 (at 30% threshold, P=.288) separated high- and low-risk patient groups. However, there were a significant difference (P values for all comparisons≤.005) and a moderate concordance (intraclass correlation, 0.645) between their Ki-67 labeling index scores. The highest concordance was found between MIB-1 and poly (concordance correlation coefficient=0.785) antibodies. None of the antibodies except Ki-67 labeling index as detected by poly (P=.031) at 20% threshold and lymph node status (P<.001) were significantly linked to disease-free survival in multivariate analysis. At 30% threshold, this was reduced to lymph node status (P<.001) alone. Our results showed that there are considerable differences between the different Ki-67 antibodies in their capacity to detect proliferating tumor cells and to separate low- and high-risk breast cancer patient groups.
尽管有几种抗体可用于免疫组织化学检测Ki-67，但即使是最常用的MIB-1也尚未得到验证。我们的目的是比较5种市售抗体在检测Ki-67方面的一致性及其预测乳腺癌预后的能力。组织微阵列由378例乳腺癌患者的代表性福尔马林固定、石蜡包埋肿瘤块构建而成。使用5种抗体检测Ki-67表达：采用显色检测的MIB-1和免疫荧光标记的MIB-1、SP-6、30-9、poly和B56。由2名病理学家在数字化玻片上独立进行半定量评估。为比较这5种抗体，使用了组内相关系数和一致性相关系数。除免疫荧光标记的MIB-1（在20%和30%阈值时，P分别为0.993和0.342）和B56（在30%阈值时，P = 0.288）外，所有抗体均能区分高风险和低风险患者组。然而，它们的Ki-67标记指数评分之间存在显著差异（所有比较的P值≤0.005）和中等一致性（组内相关系数，0.645）。MIB-1和poly抗体之间的一致性最高（一致性相关系数 = 0.785）。在多变量分析中，除poly检测的Ki-67标记指数在20%阈值时（P = 0.031）和淋巴结状态（P < 0.001）外，没有一种抗体与无病生存期显著相关。在30%阈值时，这一关联仅降至淋巴结状态（P < 0.001）。我们的结果表明，不同的Ki-67抗体在检测增殖肿瘤细胞以及区分低风险和高风险乳腺癌患者组的能力方面存在相当大的差异。
