Identification and meta-analysis of a small gene expression signature for the diagnosis of estrogen receptor status in invasive ductal breast cancer.
In breast cancer, the determination of estrogen receptor (ER) expression is crucial for the decision on therapeutic strategies. Current ER expression analysis is based on immunohistochemical (IHC) staining of ER on formalin fixed tissue sections. However, low levels of ER expression frequently escape detection because of varying sensitivities of routine histopathological laboratories. Moreover, in estimating ER by IHC the receptor protein only is tested instead of the complex underlying ER pathway, which reflects its biological activity. To overcome this limitation, we have used the microarray technology to study 56 samples of invasive ductal carcinoma. We infer a robust and reliable signature of 10 genes, which is associated with ER expression and presumably therapeutically relevant biological processes. In a meta-analysis, the signature was tested on 3 further independent microarray gene expression data sets, covering different laboratories, array platforms, and clinics. The classification based on the signature showed a very low misclassification rate. In summary, the expression of few genes is sufficient to determine ER status. Future decisions on antiestrogen based therapy in breast cancer could be based on this signature rather than on immunostaining alone.
Schneider
Jörg
J
Division of Molecular Genome Analysis, German Cancer Research Center, Heidelberg 69120, Germany.
Ruschhaupt
Markus
M
Buness
Andreas
A
Asslaber
Martin
M
Regitnig
Peter
P
Zatloukal
Kurt
K
Schippinger
Walter
W
Ploner
Ferdinand
F
Poustka
Annemarie
A
Sültmann
Holger
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D027682:Cation Transport Proteins / Q000235:genetics; D016000:Cluster Analysis; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D015203:Reproducibility of Results
D027682:Cation Transport Proteins; C496499:FOXA1 protein, human; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D051541:Hepatocyte Nuclear Factor 3-alpha; D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; C418627:SLC39A6 protein, human