[1934] Loss of Heterozygosity (LOH) and the Fractional Mutation Index (FMI) in Subtypes of Breast Cancer

Xiaoqi Lin, Sydney D Finkelstein, Jan F Silverman, Stephen Rohan, Bing Zhu. Northwestern University, Chicago; RedPath Integrated Pathology Inc., Pittsburgh; Allegheny General Hospital, Pittsburgh

Background: Based on gene expression profiles, breast cancer (BC) has classically been divided into distinct subtypes, including luminal A (LA), luminal B (LB), HER2 and basal-like (BL). Immunophenotyping (IHC) using ER, PR and HER2 correlates well with these molecular categories and is used as a surrogate method for subtyping BC. Our goal was to evaluate LOH and FMI in BC subtypes.
Design: Analysis of LOHs targeting 10 tumor suppressor genes was performed using DNA isolated from 36 BCs subtypied using ER, PR, and HER2 IHC (24 LA, 5 LB, 3 HER2 and 3 BL). FMI was defined as the total # of mutated markders/total # of informative markers.
Results: See Tables.

Table 1. Tumor sizes, nuclear grades, LOHs and FMR of BC subtypes
  Size (cm)Nuclear GradeLOHFMI
subtypesLA (n=24)1.9±1.42.1±0.73.4±1.70.30±0.15
 LB (n=5)4.0±2.93.0±0.04.4±2.70.33±0.19
 HER2 (n=3)2.3±1.03.0±0.01.0± 0.00.10±0.00
 BL (n=3)2.8±1.72.7±0.63.7±1.50.27±0.11
P valueLA vs. LB0.0260.010  
 LA vs. HER2 0.0440.0130.018
 LA vs. BL    
 LB vs. HER2  0.0790.085
 LB vs. BL    
 HER2 vs. BL  0.0390.053
student T test



Table 2. LOHs in BC subtypes
LOHLALBHER2BLP value
1p34-3611/24(46%)2/5(40%)0/2(0%)1/3(33%)P(HER2-BL)<0.05
3p24-2610/21(48%)2/5(40%)0/2(0%)2/3(67%)P(HER2-BL)<0.05
5q239/23(39%)1/5(20%)0/3(0%)0/3(0%) 
9p2110/23(44%)4/5(80%)1/3(33%)1/3(33%)P(LA-LB)<0.05
10q2311/22(50%)2/4(50%)0/3(0%)1/3(33%)P(HER2-BL)<0.05
17p137/24(29%)2/5(40%)1/3(33%)1/3(33%) 
17q124/7(57%)1/2(50%)NA1/2(50%) 
17q219/18(50%)2/4(50%)1/1(100%)0/3(0%)P(LB-HER2)<0.05
21q224/15(27%)1/4(25%)0/3(0%)1/3(33%)P(HER2-BL)<0.05
2q134/13(31%)1/5(20%)0/3(0%)1/2(50%)P(HER2-BL)<0.05
Yate's corretion test


Conclusions: 1. Different LOH profiles were seen in 4 subtypes, supporting the previously described molecular and IHC classifications.
2. Tumor size and nuclear grade of LB were significantly larger or higher respectively than LA, and LOHs and FMI were also slightly higher, suggesting the greater aggressiveness of LB than LA is possibly related to higher LOHs and FRI.
3. Nuclear grade of HER2 was higher than LA, however, LOHs and FRI were significantly lower than LA and BL. This data suggest that mechanisms other than LOHs play an important role in HER2.
4. Some LOHs were shared by all subtypes. LOH at 9p21 was higher in LB than in LA. LOHs at 1p34-36, 3p24-26, 5q23, 10q23, 21q22 and 2q13 were not detected in HER2.
Category: Pathobiology

Wednesday, March 21, 2012 9:30 AM

Poster Session V # 277, Wednesday Morning

 

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