[342] 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.

Table 1. Correlation between MIB1 and Recurrence Score

	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

Conclusions: MIB1 staining detects expression of the proliferation marker Ki-67. Our study demonstrated increased Ki-67 expression in high grade cancers and in tumors with angiolymphatic invasion. Additionally, we identified a significant association between Ki-67 expression and Oncotype Dx RS. This observation suggests that Ki-67, in conjunction with other readily available prognostic markers, may provide useful prognostic information when the Oncotype Dx RS is unavailable.
Category: Breast

Tuesday, March 23, 2010 1:45 PM

Platform Session: Section B, Tuesday Afternoon