title: Implementation of TMA and digitalization in routine diagnostics of breast pathology.
abstract: To ensure optimal treatment of breast cancer patients, breast tumours are classified based on clinico-pathological features. As part of this process, routine diagnostics of breast tumours includes histological typing and grading, as well as profiling by use of an immunohistochemistry panel of antibodies, probes and in situ hybridization. This will, as a minimum, include assessment of oestrogen receptor (OR) and HER2. The individual preparation and staining of many breast tumours in a large laboratory with this standard panel is thus time consuming and costly. Herein, we show that in breast cancer routine diagnostics the use of the tissue microarray technique in combination with digitalization of the stained multi-slides is not only economical, with a considerable cost reduction, but it also enhances standardization of tumour profiling. We demonstrate that 2 mm breast tumour cores correlate with the corresponding tumour on whole mount slides, regarding staining/hybridizing results with the biomarkers in our panel consisting of human epidermal growth factor receptor 2, OR and Topiomerase IIa. Furthermore, we show that simultaneous staining/hybridizing of multiple breast tumour specimens reduces variation of staining/hybridizing quality, hereby increasing reliability of interpretation. By scanning and digitalization of the stained and hybridized multi-slides, we could optimize documentation and filing of the results. Our work is an example of translational research by implementing a tool in daily diagnostics originally developed for high throughput analyses in the search for prognostic and predictive markers in targeted medicine.
authors.affiliation: Department of Pathology, Rigshospitalet, Copenhagen, Denmark. henrik.holm.rossing@rh.regionh.dk
authors.forename: Henrik Holm
authors.initials: HH
authors.lastname: Rossing
authors.forename: Maj-Lis Møller
authors.initials: ML
authors.lastname: Talman
authors.forename: Anne-Vibeke
authors.initials: AV
authors.lastname: Laenkholm
authors.forename: Vera Timmermans
authors.initials: VT
authors.lastname: Wielenga
mesh_terms: D000951:Antigens, Neoplasm / Q000032:analysis / Q000235:genetics; D001940:Breast / Q000473:pathology*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000473:pathology*; D004250:DNA Topoisomerases, Type II / Q000032:analysis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D017404:In Situ Hybridization, Fluorescence; D008853:Microscopy / Q000379:methods; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D013194:Staining and Labeling / Q000379:methods; D046888:Tissue Array Analysis / Q000379:methods*
chemical_list: D000951:Antigens, Neoplasm; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; C508053:ERBB2 protein, human