Ki-67 Image Cytometric Quantitation and Oncotype Dx Recurrence Score in Estrogen Receptor-Positive Breast Cancer
DJ Williams, C Cohen, M Darrow, AJ Page, B Chastain, A Adams. Emory University, Atlanta, GA
Background: The prognosis of patients with breast cancer has traditionally been determined by assessing clinicopathologic features such as lymph node metastasis, tumor size, and histologic grade. Recently, the 21-gene assay Oncotype Dx has been used in lymph node-negative, estrogen receptor (ER)-positive breast cancer to refine prognosis and direct therapy. Its utility, however, is limited by its cost, proprietary nature, and lengthy turnaround time. Ki-67 is a proliferation marker whose expression can rapidly and inexpensively be characterized by immunohistochemistry. Our aim is to correlate the expression of Ki-67 with the Oncotype Dx Recurrence Score (RS) and other prognostic indicators.
Design: ER-positive invasive breast carcinomas from 130 patients with Oncotype DX RS testing over a 2 year period were selected. Representative 5 micron tumor sections were stained with MIB1 (Dako, Carpinteria, CA), a monoclonal antibody that reacts against Ki-67. MIB1 nuclear staining was quantitated using the Automated Cellular Imaging System III (Dako). The percentage of MIB1-positive cells was assessed in ten random 40x fields, and the average was used to rate MIB1 staining as low (<10%), intermediate (10-20%), or high (>20%). MIB1 staining was compared with the Oncotype Dx RS (low [<18], intermediate [18-30], or high [>30]) and clinicopathologic parameters including grade, angiolymphatic invasion, lymph node metastasis, and tumor size.
Results: MIB1 staining was low in 36.9% (48/130) of cases, intermediate in 36.9% (48/130), and high in 26.1% (34/130). There were significant associations between MIB1 staining and Oncotype Dx RS (P=0.02; Table 1), grade (P<0.001), and angiolymphatic invasion (P=0.01). Lymph node metastasis and tumor size were not associated with MIB1.
|Low RS||Intermediate RS||High RS||P-value|
|Low MIB1||64.6% (31/48)||33.3% (16/48)||2.1% (1/48)|
|Intermediate MIB1||47.9% (23/48)||39.6% (19/48)||12.5% (6/48)|
|High MIB1||35.3% (12/34)||35.3% (12/34)||29.4% (10/34)||P=0.02|