[333] Does Nottingham Grade, MIB-1 Labeling Index (LI) Predict Recurrence Score (RS) of Oncotype Dx Assay?

Z Zhang, R Shamanna, U Raju, A Ormsby, D Chitale. Henry Ford Hospital, Detroit, MI

Background: Oncotype Dx^TM assay, a RT-PCR based genomic assay analyzes the expressions of 21 genes to give a distant breast cancer RS, stratifying estrogen receptor (ER)+, node negative breast cancer patients for or against chemotherapy. In the literature, reports correlating histopathologic parameters correlating with Oncotype Dx^TM RS independent of Genomic Health are limited. Here we present our experience with correlation of traditional histopathologic variables with RS.
Design: 48 cases of invasive breast cancers with Oncotype Dx data were evaluated. Clinical and morphologic findings including histologic subtype, Nottingham grade, TMN stage, ER, PR, Her2/neu status were recorded. Tissue microarray block was constructed from formalin fixed paraffin embedded tumor blocks containing duplicate, 0.6 mm cores. Immunostaining was performed using Ki-67/MIB antibody. LI was scored as percent positive tumor nuclei and were grouped into low (<25%) and high (>=25%). Statistical analysis was performed by using Chi square test and Spearman correlation. (P-value<0.05significant).
Results: Out of 48 invasive carcinomas, there were 38 ductal, 8 lobular, 1 mucinous, and 1 tubular. 17/48 (35.4%) cases were grade1, 24/48 (50%) grade 2, 7/48 (14.6%) grade 3. Distribution of MIB1 LI against grade and RS are shown in Tables1,2. RS ranged from 4-39 (mean 18) with 23/48 (47.9%) in low risk, 22/48 (45.8%) intermediate risk and 3/48 (6.3%) high risk. Overall, there was no statistical correlation between grade, MIB1 LI with RS. 5 cases had metastatic lymph nodes (4 micrometastasis): 1 high RS, grade3, low MIB-1 LI; 1 intermediate RS, grade1, high MIB1 LI and 3 low RS, grade1/2, low MIB-1LI.

Table 1

MIB-1 LI	Grade 1	Grade 2	Grade 3
Low (n=39)	15	18	6
High (n=9)	2	6	1
Total (n=48)	17	24	7

Table 2

MIB-1 LI	Low RS	Intermediate RS	High RS
Low (n=39)	21	15	3
High (n=9)	2	7	0
Total (n=48)	23	22	3

Conclusions: Our results confirm heterogeneity within ER+ node negative breast cancers. We identified a subset of patients having low RS with high grade (2/3) and MIB-1 LI who may benefit from additional treatment. Tumor grade and MIB1 LI complement RS score in a subset and these findings may have utility in health systems that have limitations on performing Oncotype DX due to higher cost. In cases with low MIB-1 LI and/or low grade, Oncotype DX identified high risk tumors(6 intermediate, 1 high RS) making it an independent indicator for clinical decision making. Although currently Oncotype DX is not recommended for node+ tumors, 60% of node+ cases had low RS.
Category: Breast

Monday, March 9, 2009 9:30 AM

Poster Session I Stowell-Orbison/Autopsy Award # 56, Monday Morning