1. This paper describes the advantages of the TMA method combined with digitalization in routine diagnostics of breast pathology. The authors, using our TMA Master tissue microarrayer and Pannoramic MIDI digital slide scanner, concluded that the implementation of the TMA method in combination with digitalization in the routine diagnostics of breast cancer patients is a reliable and economical tool for tumour classification.
Rossing, H.H., Talman, M.-L.M., Lænkholm, A.-V., and Wielenga, V.T. (2012).
Implementation of TMA and digitalization in routine diagnostics of breast pathology.
APMIS 120, 341–347.
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.
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2. This methodology article describes a study about the optimization of TMA construction. The authors constructed TMA blocks, using our TMA Master device, taking recipient blocks made from nine different paraffin types. TMA blocks prepared by the method described in this article can be pre-cooled and sectioned as regular FFPE tissue blocks, and form ribbons that spread easily on a water bath. The authors concluded that: quality TMA sections prepared this way can be used for a variety of assays with manual and automated platforms.
Chang, H., Peluso, D., Hussain, S., Shipitsin, M., and Blume-Jensen, P. (2014).
Optimizing tissue microarray construction procedure to improve quality of sections.
J. Histotechnol. 37, 95–100.
Abstract
Tissue microarray (TMA) technology makes it possible to perform high throughput in situ analysis of tissue samples, and has become a powerful tool in multiple fields of life sciences. However, obtaining high-quality TMA sections can be technically challenging. In this paper, two aspects of TMA construction were investigated, namely, the paraffin type of the recipient block and the tempering method to facilitate donor core integration. Nine commonly used paraffin types were evaluated, and four were identified with satisfactory performance. It was also found that, after TMA construction, 1-hour incubation at 50°C significantly improved the integration of donor cores with the recipient block. Large TMA blocks prepared with the described method were easy to section and yielded high quality TMA slides.
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3. The TMA technique is often used for biomarker discoveries. In this study the authors constructed 21 TMAs using our TMA Master tissue microarrayer. They extracted three tissue core biopsies of 0.6 mm in diameter from morphologically representative areas of all FFPE donor blocks. The authors concluded that the expression of AURKA protein is a molecular biomarker with prognostic value for patients with CRCLM.
Goos, J. a. C.M., Coupe, V.M.H., Diosdado, B., Delis-Van Diemen, P.M., Karga, C., Beliën, J. a. M., Carvalho, B., van den Tol, M.P., Verheul, H.M.W., Geldof, A.A., et al. (2013).
Aurora kinase A (AURKA) expression in colorectal cancer liver metastasis is associated with poor prognosis.
Br. J. Cancer 109, 2445–2452.
Abstract
Background: Five-year survival after resection of colorectal cancer liver metastasis (CRLCM) is < 30%. We recently found that aurora kinase A (AURKA) drives 20q gain-associated tumour progression and is associated with disease recurrence. This study evaluates the prognostic value of AURKA expression in CRCLM of patients who underwent liver resection.
Methods: Tissue microarrays (TMAs) were generated using formalin-fixed paraffin-embedded CRCLM and matched primary tumour from a multi-institutional cohort of patients with CRCLM who underwent liver resection between 1990 and 2010. Tissue microarrays were stained for AURKA using immunohistochemistry, and a hazard rate ratio (HRR) for the association between overall survival (OS) and nuclear AURKA expression in CRCLM was calculated. Results were validated by 500-fold cross-validation.
Results: The expression of AURKA was evaluated in CRCLM of 343 patients. High AURKA expression was associated with poor OS (HRR 1.55, P<0.01), with a cross-validated average HRR of 1.57 (P=0.02). Average HRR was adjusted for the established prognostic clinicopathological variables in a multivariate analysis (average HRR 1.66; P=0.02). The expression of AURKA in CRCLM was correlated to its expression in corresponding primary tumour (P<0.01).
Conclusion: The expression of AURKA protein is a molecular biomarker with prognostic value for patients with CRCLM, independent of established clinicopathological variables.
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