Molecular heterogeneity of inflammatory breast cancer: a hyperproliferative phenotype.
OBJECTIVE
Inflammatory breast cancer (IBC) is associated with very poor prognosis. The aims of this study are (a) to prospectively identify differential gene expression patterns associated with IBC and (b) to confirm these pathways using tissue arrays.


METHODS
For gene expression analysis, IBC (n=14) was clinically defined as rapid-onset cancer associated with erythema and skin changes, whereas non-IBC patients (n=20) had stage III breast cancers, and cDNA analysis was carried out using the Affymetrix (Santa Clara, CA) HG-U133A microarrays. Tissue arrays were constructed from paraffin-embedded material, and the molecular phenotype of 75 IBC was compared with results from>2,000 non-IBC.


RESULTS
Gene expression analyses indicated that IBC has higher expression of genes associated with increased metabolic rate, lipid signaling, and cell turnover relative to non-IBC tumors. Consistent with the expression analysis, IBC had statistically higher Ki-67 (93% versus 11%; P<0.001). BAX expression, reflecting increased apoptosis and cell turnover, was significantly uniformly higher in almost all IBC (98% versus 66%; P<0.05), whereas the expression of Bcl-2 was not significantly different. IBC tumors were more likely to be steroid hormone receptor negative (estrogen receptor, 49% versus 30%; P=0.002; progesterone receptor, 68% versus 42%; P=0.001). The expression of tyrosine kinases was not significantly different. E-cadherin was found to be expressed in 87% of IBC, whereas the expression p53 was not significantly different.


CONCLUSIONS
This study is one of the largest molecular analyses of IBC. Both IBC and non-IBC are genetically heterogeneous with consistent differences in the molecular phenotype of IBC.
Nguyen
Dang M
DM
Breast Center, Baylor College of Medicine and the Methodist Hospital, Houston, Texas 77030, USA.
Sam
Kathy
K
Tsimelzon
Anna
A
Li
Xiaoxian
X
Wong
Helen
H
Mohsin
Syed
S
Clark
Gary M
GM
Hilsenbeck
Susan G
SG
Elledge
Richard M
RM
Allred
D Craig
DC
O'Connell
Peter
P
Chang
Jenny C
JC
D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D018740:Genetic Heterogeneity; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010375:Pedigree; D010641:Phenotype