Standardization for Ki-67 Assessment in Moderately Differentiated Breast Cancer. A Retrospective Analysis of the SAKK 28/12 Study

被引:32
作者
Varga, Zsuzsanna [1 ]
Cassoly, Estelle [2 ]
Li, Qiyu [2 ]
Oehlschlegel, Christian [3 ]
Tapia, Coya [4 ]
Lehr, Hans Anton [5 ]
Klingbiel, Dirk [2 ]
Thuerlimann, Beat [2 ,6 ]
Ruhstaller, Thomas [6 ]
机构
[1] Univ Zurich Hosp, Inst Surg Pathol, CH-8091 Zurich, Switzerland
[2] Swiss Grp Clin Canc Res, Bern, Switzerland
[3] Cantonal Hosp St Gallen, Inst Pathol, St Gallen, Switzerland
[4] Univ Bern, Inst Pathol, Bern, Switzerland
[5] Inst Pathol, Friedrichshafen, Friedrichshafen, Germany
[6] Cantonal Hosp St Gallen, Breast Ctr, St Gallen, Switzerland
来源
PLOS ONE | 2015年 / 10卷 / 04期
关键词
INTERNATIONAL EXPERT CONSENSUS; PREDICTIVE-VALUE; PRIMARY THERAPY; LABELING INDEX; KI67; PROLIFERATION; REPRODUCIBILITY; HIGHLIGHTS; WOMEN;
D O I
10.1371/journal.pone.0123435
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background Proliferative activity (Ki-67 Labelling Index) in breast cancer increasingly serves as an additional tool in the decision for or against adjuvant chemotherapy in midrange hormone receptor positive breast cancer. Ki-67 Index has been previously shown to suffer from high inter-observer variability especially in midrange (G2) breast carcinomas. In this study we conducted a systematic approach using different Ki-67 assessments on large tissue sections in order to identify the method with the highest reliability and the lowest variability. Materials and Methods Five breast pathologists retrospectively analyzed proliferative activity of 50 G2 invasive breast carcinomas using large tissue sections by assessing Ki-67 immunohistochemistry. Ki-67-assessments were done on light microscopy and on digital images following these methods: 1) assessing five regions, 2) assessing only darkly stained nuclei and 3) considering only condensed proliferative areas ('hotspots'). An individual review (the first described assessment from 2008) was also performed. The assessments on light microscopy were done by estimating. All measurements were performed three times. Inter-observer and intra-observer reliabilities were calculated using the approach proposed by Eliasziw et al. Clinical cutoffs (14% and 20%) were tested using Fleiss' Kappa. Results There was a good intra-observer reliability in 5 of 7 methods (ICC: 0.76-0.89). The two highest inter-observer reliability was fair to moderate (ICC: 0.71 and 0.74) in 2 methods (region-analysis and individual-review) on light microscopy. Fleiss'-kappa-values (14% cut-off) were the highest (moderate) using the original recommendation on light-microscope (Kappa 0.58). Fleiss' kappa values (20% cut-off) were the highest (Kappa 0.48 each) in analyzing hotspots on light-microscopy and digital-analysis. No methodologies using digital-analysis were superior to the methods on light microscope. Conclusion Our results show that all methods on light-microscopy for Ki-67 assessment in large tissue sections resulted in a good intra-observer reliability. Region analysis and individual review (the original recommendation) on light-microscopy yielded the highest inter-observer reliability. These results show slight improvement to previously published data on poor-reproducibility and thus might be a practical-pragmatic way for routine assessment of Ki-67 Index in G2 breast carcinomas.
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页数:13
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