title: Genome-wide gene expression profiling of formalin-fixed paraffin-embedded breast cancer core biopsies using microarrays.
abstract: The routine workflow for invasive cancer diagnostics includes biopsy processing by formalin fixation and paraffin embedding. It has been shown only recently that this kind of sample can be used for gene expression analysis with microarrays. To support this view, the authors conducted a microarray study using formalin-fixed paraffin-embedded (FFPE) core needle biopsies from breast cancers. Typically, for the 3'-biased chip type that was used, the probe sets interrogate sequences near the poly-A-tail of the transcripts, and this kind of probe turned out to be suitable to measure RNA levels in FFPE biopsies. For ER and HER2, the authors observed strong correlations between RNA levels and protein expression (p = 0.000003 and p = 0.0022). ER and HER2 classification of the biopsies by the RNA levels was feasible with high sensitivity and specificity (AUROC = 0.93 and AUROC = 0.96). Furthermore, a signature of 346 genes was identified that correlated with ER and a signature of 528 genes that correlated with HER2 protein status. Many of these genes (ER: 63%) could be confirmed by analysis of gene expression data from frozen tissues. The findings support the notion that clinically relevant information can be gained from microarray analyses of FFPE cancer biopsies. This opens new opportunities for biomarker detection studies and the integration of microarrays into the workflow of cancer diagnostics.
authors.affiliation: Institute of Pathology, Charité-Universitätsmedizin Berlin, Germany. jan.budczies@charite.de
authors.forename: Jan
authors.initials: J
authors.lastname: Budczies
authors.forename: Wilko
authors.initials: W
authors.lastname: Weichert
authors.forename: Aurelia
authors.initials: A
authors.lastname: Noske
authors.forename: Berit Maria
authors.initials: BM
authors.lastname: Müller
authors.forename: Claudia
authors.initials: C
authors.lastname: Weller
authors.forename: Timo
authors.initials: T
authors.lastname: Wittenberger
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hofmann
authors.forename: Manfred
authors.initials: M
authors.lastname: Dietel
authors.forename: Carsten
authors.initials: C
authors.lastname: Denkert
authors.forename: Volker
authors.initials: V
authors.lastname: Gekeler
mesh_terms: D001707:Biopsy, Needle / Q000379:methods*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D016000:Cluster Analysis; D047628:Estrogen Receptor alpha / Q000235:genetics; D005240:Feasibility Studies; D005557:Formaldehyde / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods*; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D016612:Paraffin Embedding / Q000379:methods*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D025341:Principal Component Analysis; D011786:Quality Control; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D012189:Retrospective Studies; D016707:Tissue Fixation / Q000379:methods*
chemical_list: D047628:Estrogen Receptor alpha; D005557:Formaldehyde; D012313:RNA; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human