The Core of the Problem
Next generation tissue microarrays overcome punching inaccuracies and bring the technique into the era of precision medicine
Inti Zlobec |
At a Glance
- Tissue microarrays (TMAs) are increasingly used for biomarker evaluation and validation
- Conventional TMAs lack accuracy in punching, meaning that some areas of interest are captured inadequately or not at all
- Next generation TMAs (ngTMAs) are digitally scanned, annotated and cored, resulting in more precise alignment and better coring to optimize research
- Now that we’ve achieved precision coring, the next step for ngTMAs is to multiplex antibodies and improve image analysis
As the era of precision medicine dawns, the role of the pathologist is extending beyond diagnosis to include the interpretation of molecular tissue biomarkers. The ability to detect protein, RNA and DNA alterations in cancer now helps us to tailor prognoses and predict therapy responses. As a consequence, biomarker research has exploded over recent years – and with it, the number of studies using tissue microarrays (TMAs) as a tool for biomarker evaluation and validation. Essentially, the TMA is a tissue archive constructed by transferring small tissue cores, typically 0.6 or 1.0 mm in diameter, from a “donor” tissue block into a “recipient” block. Repeated multiple times, a recipient TMA block can carry up to 500 different tissue cores from multiple tumors or patients (Figure 1).
In 1998, Kononen et al. (1) published the first report using TMAs for high-throughput molecular profiling of cancers; at the same time, the report highlighted some of the technique’s great advantages. First and foremost, the high-throughput nature of the approach means that studies on a large number of patient tissues can be assembled on just a handful of TMA blocks. This can substantially reduce the cost of consumables, and can help prevent the depletion of tissue that should remain in the diagnostic archive for eventual re-evaluation. Staining procedures can be carried out simultaneously across different cores, eliminating experimental variability. Dozens of different biomarkers can be applied to serial sections of the TMA, ensuring its viability as a longstanding research tool for many study groups. Attributes like these mean that TMAs have become a mainstay in translational research.
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