Research article
Prognostic value of proliferation assay in the luminal, HER2-positive, and triple-negative biologic classes of breast cancer
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* Corresponding author: Emad A Rakha emadrakha@yahoo.com
1 Department of Histopathology, School of Molecular Medical Sciences, Queens Medical Centre, University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham, NG7 2UH, UK
2 Pathology Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia Governorate, Egypt
3 Occupational Health, School of Molecular Medical Sciences, Queens Medical Centre, University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham, NG7 2UH, UK
4 Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, UK
Breast Cancer Research 2012, 14:R3 doi:10.1186/bcr3084
Published: 6 January 2012Abstract
Introduction
Although the prognostic significance of proliferation in early invasive breast cancer has been recognized for a long time, recent gene-expression profiling studies have reemphasized its biologic and prognostic value and the potential application of its assessment in routine practice, particularly to define prognostic subgroups of luminal/hormone receptor-positive (HR+) tumors. This study aimed to assess the prognostic value of a proliferation assay by using Ki-67 immunohistochemistry as compared with mitotic count scores.
Method
Proliferation was assessed by using Ki-67 labeling index (Ki-67LI) and mitotic scores in a large (n = 1,550) and well-characterized series of clinically annotated primary operable invasive breast cancer with long-term follow-up. Tumors were phenotyped based on their IHC profiles into luminal/HR+, HER2+, and triple-negative (TN) classes. We used a split-sample development and validation approach to determine the optimal Ki-67LI cut-offs.
Results
The optimal cut-points of Ki-67LI were 10% and 50% for the luminal class. Both Ki7LI and MS were able to split luminal tumors into subgroups with significantly variable outcomes, independent of other variables. Neither mitotic count scores nor Ki-67LI was associated with outcome in the HER2+ or the TN classes.
Conclusions
Assessment of proliferation by using Ki-67LI and MS can distinguish subgroups of patients within luminal/hormone receptor-positive breast cancer significantly different in clinical outcomes. Overall, both Ki-67 LI and mitotic-count scores showed comparable results. The method described could provide a cost-effective method for prognostic subclassification of luminal/hormone receptor-positive breast cancer in routine clinical practice.