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 DxTM 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 DxTM 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.
|MIB-1 LI||Grade 1||Grade 2||Grade 3|
|MIB-1 LI||Low RS||Intermediate RS||High RS|
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.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 56, Monday Morning