PMC:4996397 / 1521-5868 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/4996397","sourcedb":"PMC","sourceid":"4996397","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4996397","text":"1. Introduction: TMA Technology and Statistical Considerations\nTissue microarray (TMA) technology was first described by Battifora et al. [1] in 1986 as a ‘sausage’ block method to prepare multi tissue sections; it was used and modified by Wan et al. [2] in 1987, introducing the cannula, and further developed as a device that could rapidly produce TMA with regular shape and defined tissue size by Kononen [3] et al. in 1998. In the last fifteen years, technological progress and extensive biological and medical knowledge improvements are inducing researchers to continuously investigate putative diagnostic, prognostic and therapeutic biomarkers [4]. Traditional histopathology techniques are often unacceptably time consuming, extremely labor intensive and very expensive [5], while TMAs are a powerful tool to overcome many of these challenges and are often used for characterization of antibodies, tissue and disease specific epidemiological expression profiling of proteins via immunohistochemistry (IHC) and genes via in situ hybridization, respectively. Therefore, TMAs are more and more becoming the method of choice for large scale and epidemiological biomarkers investigations. IHC analyses of such TMAs have the great advantage to minimalize all the intra-laboratory differences in staining procedures, as well as the inter‑observer evaluation variability. Moreover, TMAs can even be constructed from paraffin needle biopsy specimens and also allow testing the expression of biomarkers on the following slides of a constructed TMA block for studying markers co-expressions [6,7,8,9,10,11,12,13]. \nSubsequently, several instruments were developed reaching more and more technical improvements. These include the TMA Master® (TMA-M; 3D-Histech Ltd, Sysmex Suisse AG, Horgen, Switzerland) and more recently a unique today’s available system: the TMA GrandMaster® (TMA-GM; 3D-Histech Ltd, Sysmex Suisse AG). Today, the TMA-GM is the most automated and sophisticated device for the construction of TMAs, allowing the precise selection of specific regions of interest (ROI) on the donor blocks. It detects the depth of the donor blocks and drills each time the most appropriate hole in the empty paraffin recipient blocks. It acquires a tissue carrot from the donor blocks and places it at the assigned coordinate (X-Y) and it allows the construction of up to 12 recipient blocks in parallel. Thanks to the high precision of this instrument, we hypothesized and demonstrated that previously prepared TMAs (independently from their mode of construction) could be used as donor blocks in order to transfer special tissue cores, when necessary.\nWhen planning a new study, histological, statistical and logistical aspects must be considered [14,15,16,17]. These comprehend tissue type, specific histological regions and cell types for inclusion in the TMA, the number of tissue spots, sample size, and statistical analysis [18,19]. Quality of the samples and sample size represent the most challenging issue encountered and are often limiting the investigation. Moreover, it happens that information at time of planning is insufficient and/or that during the performance of such a study—thanks to knowledge resulting in the course of the study itself or concomitantly discovered by others—subpopulations of particular scientific and medical interest are identified [20]. Thanks to the general improvement of all technologies, leading to brighter biomedical knowledge, these rare cohorts of patients become increasingly topic of new research interest, though in general still not predictable at time of TMA design [21,22,23,24]. Statistical power of analysis based on, for example, future therapy response rate of a certain patient cohort could probably reveal the need to select tissues of certain patients from existing, ongoing studies and group them into a new one for obtaining significant results. In that case processing of such tissue cores could be essential for the successful performance of a new clinically relevant study and otherwise wasted if not specifically used on the original TMA. With this purpose we planned the following experiments for tissue core “transplantation” and defined optimal conditions for the construction of new “elastic” TMAs. To our knowledge no other work along these lines has previously been performed.","divisions":[{"label":"Title","span":{"begin":0,"end":62}}],"tracks":[{"project":"2_test","denotations":[{"id":"27600223-3525985-69477641","span":{"begin":139,"end":140},"obj":"3525985"},{"id":"27600223-3655378-69477642","span":{"begin":252,"end":253},"obj":"3655378"},{"id":"27600223-9662379-69477643","span":{"begin":409,"end":410},"obj":"9662379"},{"id":"27600223-16782284-69477644","span":{"begin":651,"end":652},"obj":"16782284"},{"id":"27600223-17723364-69477645","span":{"begin":778,"end":779},"obj":"17723364"},{"id":"27600223-24681739-69477646","span":{"begin":1588,"end":1589},"obj":"24681739"},{"id":"27600223-21293543-69477647","span":{"begin":1590,"end":1591},"obj":"21293543"},{"id":"27600223-17440968-69477648","span":{"begin":1592,"end":1593},"obj":"17440968"},{"id":"27600223-17721278-69477649","span":{"begin":1594,"end":1595},"obj":"17721278"},{"id":"27600223-23792768-69477650","span":{"begin":1596,"end":1598},"obj":"23792768"},{"id":"27600223-20403031-69477651","span":{"begin":1599,"end":1601},"obj":"20403031"},{"id":"27600223-20591915-69477652","span":{"begin":1602,"end":1604},"obj":"20591915"},{"id":"27600223-23907597-69477653","span":{"begin":1605,"end":1607},"obj":"23907597"},{"id":"27600223-24694642-69477654","span":{"begin":2746,"end":2748},"obj":"24694642"},{"id":"27600223-20921484-69477655","span":{"begin":2752,"end":2754},"obj":"20921484"},{"id":"27600223-21615936-69477656","span":{"begin":2755,"end":2757},"obj":"21615936"},{"id":"27600223-14725164-69477657","span":{"begin":2928,"end":2930},"obj":"14725164"},{"id":"27600223-14621358-69477658","span":{"begin":2931,"end":2933},"obj":"14621358"},{"id":"27600223-21796190-69477659","span":{"begin":3370,"end":3372},"obj":"21796190"},{"id":"27600223-12746740-69477660","span":{"begin":3618,"end":3620},"obj":"12746740"},{"id":"27600223-22729463-69477661","span":{"begin":3621,"end":3623},"obj":"22729463"},{"id":"27600223-21087535-69477662","span":{"begin":3624,"end":3626},"obj":"21087535"},{"id":"27600223-19880283-69477663","span":{"begin":3627,"end":3629},"obj":"19880283"}],"attributes":[{"subj":"27600223-3525985-69477641","pred":"source","obj":"2_test"},{"subj":"27600223-3655378-69477642","pred":"source","obj":"2_test"},{"subj":"27600223-9662379-69477643","pred":"source","obj":"2_test"},{"subj":"27600223-16782284-69477644","pred":"source","obj":"2_test"},{"subj":"27600223-17723364-69477645","pred":"source","obj":"2_test"},{"subj":"27600223-24681739-69477646","pred":"source","obj":"2_test"},{"subj":"27600223-21293543-69477647","pred":"source","obj":"2_test"},{"subj":"27600223-17440968-69477648","pred":"source","obj":"2_test"},{"subj":"27600223-17721278-69477649","pred":"source","obj":"2_test"},{"subj":"27600223-23792768-69477650","pred":"source","obj":"2_test"},{"subj":"27600223-20403031-69477651","pred":"source","obj":"2_test"},{"subj":"27600223-20591915-69477652","pred":"source","obj":"2_test"},{"subj":"27600223-23907597-69477653","pred":"source","obj":"2_test"},{"subj":"27600223-24694642-69477654","pred":"source","obj":"2_test"},{"subj":"27600223-20921484-69477655","pred":"source","obj":"2_test"},{"subj":"27600223-21615936-69477656","pred":"source","obj":"2_test"},{"subj":"27600223-14725164-69477657","pred":"source","obj":"2_test"},{"subj":"27600223-14621358-69477658","pred":"source","obj":"2_test"},{"subj":"27600223-21796190-69477659","pred":"source","obj":"2_test"},{"subj":"27600223-12746740-69477660","pred":"source","obj":"2_test"},{"subj":"27600223-22729463-69477661","pred":"source","obj":"2_test"},{"subj":"27600223-21087535-69477662","pred":"source","obj":"2_test"},{"subj":"27600223-19880283-69477663","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#eca393","default":true}]}]}}