Tissue Microarrays in Genomic Research
Introduction
In the past 10 years, the genomic era for molecular biology and cancer research has advanced greatly due to the efforts of both national and international research centers. There are now many resources that are dedicated to the accurate annotation of the human genome that offers sensitive methods to identify alterations to the nucleic acid in states of disease and cancer. For example, complementary DNA expression profiling is used to advance dual-labeled hybridization techniques so quantitative measurements of gene function can be provided. Tissue microarrays (TMAs) that are developed by Kononen and coworkers are now a common method that is vastly used in the validation of candidate biomarkers. Formalin fixed paraffin embedded (FFPE) tissue blocks are also a huge resource that is largely untapped and has the potential to provide important insight for collaborations for histology and pathology departments.
TMAs
The power of TMA technology resides in high density and precision of clinical tissue spots. Validation studies have shown consistent protein expression along with DNA copy numbers through immunohistochemical and fluorescence in situ hybridization studies. Many studies have evaluated TMA core sampling while hundreds have utilized it for candidate marker authentication and prioritization. The TMA technique is appealing as there is precise placement of 200-600 (1.0-0.6mm) core samples into a single paraffin block. Once the sectioning is completed, tissue cores retain the same orientation which permits specimen tracking and database integration. Literature review found that there is an exponential increase of TMA applications used among the research community in the past 5 years. This increase reflects that:
· There is a critical need to authenticate biomarkers that are of prognostic significance.
· Affordable technology is very valuable.
· FFPE tissues are important in bioresearch to aid in determining prognosis of candidates.
Cancer Research
TMAs can benefit cancer research and translational genomics by increasing the utility of archival tissues used in molecular analysis. For example, TMAs have been used in in situ hybridization and fluorescence in situ hybridization. TMAs can also utilize FFPEs that have been proven to be cost effective and remain the traditional method of choice in the storage of pathological specimens and clinical trial materials. The vast number of archived FFPE blocks that can be accessed by TMAs enable an almost limitless ocean of data available. Another benefit of TMA is the cross-disciplinary efforts or almost all researchers and pathologists in standardization of assays. TMAs are most commonly used for optimization of novel immunohistochemical markers that can assess staining integrity and cellular localization at the same time by alteration of a singular experimental parameter. Before high density TMAs were available, the analysis of multiple whole tissue sections for biomarker identification and authentication were time consuming and cost prohibitive. Other methods that can achieve the same effect causes tissue disintegration and is unable to provide localization or regional specificity of markers. The TMA technique has been able to provide standardization and analysis of biomarkers for tissue morphology. The retention of tissue features enables regional characterization of specific biomarkers. This offers benefits in terms of determining prevalence and prognosis of the candidate biomarker.
Applications
TMAs are proven to be useful in clinical laboratories for histological applications as it is able to perform multiple assays on many samples. This is the reason why many academic research hospitals have TMA equipment. There are also numerous institutions that have dedicated facilities and offer services for TMA. It has become a necessity as a validation tool by being able to array hundreds of specimens that provide prognosis in newly identified biomarkers. Candidate marker molecular analyses by TMA can be facilitated through general parameters such as 10% buffered formalin fixation for 12-24 hours using standard automated tissue processing.
· To assess the role of a candidate gene in neoplastic progression, the best TMA block should contain a myriad of specimens, ideally from one institution.
· To assess marker prevalence in a specific population, specimens should be gathered from multiple blocks to provide the best data.
· To assess biomarker prevalence and prognosis for a specific tumor, the best TMA should be constructed from sequential cases that have been accumulated over time from one institution with at least attached clinical data for a duration of 5 years.
· Other applications include animal studies that uses TMA to chronicle time and treatment dependent experiments and more.
Conclusion
Many current literatures have demonstrated TMAs using paraffin medium and FFPE blocks for most studies due to the ease of specimen availability, long term storage, and cost-effectiveness for specimens. The TMA platform is an unparalleled tool to optimize assay and adapt novel molecular assays to archival paraffin tissues which are still a large and relatively untapped molecular repository. The remarkable value of TMA applications has been the efficiency and accuracy in the detection of clinicopathologic associations in a wide variety of diseases. The portability of this technique has also played a vital role in the widespread use of it and will continue to drive TMA applications.
References:
Annals of Saudi Medicine : Tissue Microarray: A rapidly evolving diagnostic and research tool.
International Journal of Case Reports and Images: Tissue Microarray: A powerful and rapidly evolving
