Comparison of the effect of different techniques for measurement of Ki67 proliferation on reproducibility and prognosis prediction accuracy in breast cancer

被引:106
作者
Gudlaugsson, Einar [1 ]
Skaland, Ivar [1 ]
Janssen, Emiel A. M. [1 ]
Smaaland, Rune
Shao, Zhiming [2 ]
Malpica, Anais [3 ,4 ]
Voorhorst, Feja [5 ]
Baak, Jan P. A. [1 ,2 ]
机构
[1] Stavanger Univ Hosp, Dept Pathol, N-4068 Stavanger, Norway
[2] Fudan Univ, Dept Breast Surg, Canc Hosp, Shanghai 200433, Peoples R China
[3] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA
[4] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA
[5] Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands
关键词
breast cancer; digital image analysis; Ki67; prognosis; proliferation; quantification; reproducibility; EXPRESSION; MARKER; INDEX; KI-67;
D O I
10.1111/j.1365-2559.2012.04329.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Gudlaugsson E, Skaland I, Janssen E A M, Smaaland R, Shao Z, Malpica A, Voorhorst F & Baak J P A ?(2012) Histopathology?Comparison of the effect of different techniques for measurement of Ki67 proliferation on reproducibility and prognosis prediction accuracy in breast cancer Aims: The proliferation factor Ki67 is prognostic in breast cancer and included in international therapy guidelines, but measurement procedures differ between laboratories. We compared the reproducibility and prognostic value of different Ki67 sampling and measurement methods. Methods and results: In 237 T1,2N0M0 breast cancers without adjuvant systemic treatment, strictly standardized section thickness, automated antigen retrieval and immunohistochemistry were used. The percentages of Ki67-positive nuclei were assessed using (i) a quick-scan rapid estimate, (ii) ocular-square-guided counts by independent pathologists, (iii) computerized point-grid-sampling interactive morphometry (CIM) and (iv) automated digital image analysis (DIA). Quick-scan rapid estimates were poorly reproducible. The optimal prognostic thresholds of Ki67 counts by two pathologists differed greatly (4%, 14%; kappa: 0.36), with many therapeutic differences. CIM-Ki67 and DIA-Ki67 were strongly prognostic (P < 0.0001) and reproducible. DIA-Ki67 (threshold: 6.5%) was the strongest and most robust prognosticator (the threshold could vary from 4 to 15% without significant prognostic loss). Ki67 was prognostically strongest in the periphery of the tumour. Conclusion: In node-negative breast cancer without adjuvant systemic treatment, Ki67% by DIA, but not subjective counts, is reproducible and prognostically strong. This casts serious doubt on therapeutic guidelines using subjective counts of Ki67.
引用
收藏
页码:1134 / 1144
页数:11
相关论文
共 19 条
[1]  
Abe O, 2005, LANCET, V366, P2087, DOI 10.1016/s0140-6736(05)66544-0
[2]  
Baak J.P. A., 1991, MANUAL QUANTITATIVE
[3]   The framework of pathology: Good Laboratory Practice by quantitative and molecular methods [J].
Baak, JPA .
JOURNAL OF PATHOLOGY, 2002, 198 (03) :277-283
[4]   Use of the St Gallen classification for patients with node-negative breast cancer may lead to overuse of adjuvant chemotherapy [J].
Boyages, J ;
Chua, B ;
Taylor, R ;
Bilous, M ;
Salisbury, E ;
Wilcken, N ;
Ung, O .
BRITISH JOURNAL OF SURGERY, 2002, 89 (06) :789-796
[5]   Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12 155 patients [J].
de Azambuja, E. ;
Cardoso, F. ;
de Castro, G., Jr. ;
Colozza, M. ;
Mano, M. S. ;
Durbecq, V. ;
Sotiriou, C. ;
Larsimont, D. ;
Piccart-Gebhart, M. J. ;
Paesmans, M. .
BRITISH JOURNAL OF CANCER, 2007, 96 (10) :1504-1513
[6]   AN ELEMENTARY INTRODUCTION TO STEREOLOGY (QUANTITATIVE MICROSCOPY) [J].
ELIAS, H ;
HYDE, DM .
AMERICAN JOURNAL OF ANATOMY, 1980, 159 (04) :411-446
[7]  
Ellis IO, 2003, PATHOLOGY GENETICS T, P18
[8]   Aspects of scanning microdensitometry I. Stray light (glare) [J].
Goldsteind, D. J. .
JOURNAL OF MICROSCOPY, 1970, 92 :1-16
[9]   THE EFFICIENCY OF SYSTEMATIC-SAMPLING IN STEREOLOGY AND ITS PREDICTION [J].
GUNDERSEN, HJG ;
JENSEN, EB .
JOURNAL OF MICROSCOPY-OXFORD, 1987, 147 :229-263
[10]   A PROGNOSTIC INDEX IN PRIMARY BREAST-CANCER [J].
HAYBITTLE, JL ;
BLAMEY, RW ;
ELSTON, CW ;
JOHNSON, J ;
DOYLE, PJ ;
CAMPBELL, FC ;
NICHOLSON, RI ;
GRIFFITHS, K .
BRITISH JOURNAL OF CANCER, 1982, 45 (03) :361-366