Tissue Microarray: A Technology that Revolutionized Research in Pathology
With the advancement of technology, there is an immense amount of information that is available on multiple expression levels of a vast number of genes obtained through high density cDNA microarrays, a platform that allows high throughput analysis of tissue samples. Tissue microarray (TMA) technology has been used in the beginning for basic research in the target authentication of cDNA and other approaches that has made TMA an invaluable technology used in clinical research. With the acceleration in the discovery of new genes and their use in variable pathways, there is more demand for the analysis if these new genes in their various stages, lesions, and tissues involved in metastasis.
Construction and Design of TMA
In the manufacturing of TMA, an automatic or manual device can be used. However, standard histopathology work is involved in the construction of TMA tissue cores. Careful attention and planning are required in the construction of TMA to maximize its benefits. TMA construction starts with the collection of data and specimens. Most TMAs are constructed through archived formalin fixed paraffin embedded specimens. The quality of TMA specimens can be represented through hematoxylin eosin stained slides. The best way to select the proper specimens for TMA is by mapping the area of interest using ink on the freshly stained slide. Both the depth and width of the tissue is important as the target is three dimensional. TMA cylindrical cores are constructed using paraffin embedded tissue that are removed from donor blocks originating from autopsy, research material, or surgery. These cylinders or cores are then inserted into a recipient block at a low meting point to prevent the formation of bubbles during the TMA process.
Applications of TMA
When it comes to the applications of the characterizations of the vast number of genes or gene clusters linked with tumors, the approach using fresh frozen specimens or formalin fixed paraffin embedded tissues are time consuming and less cost efficient. The TMA technology uses a large scale high throughput analyses of tissues. Specimens suitable to be used in TMA can be used in a broad range of applications such as:
a) Diagnostic Biomarker Validation
TMA is most commonly used in basic translational research in clinical samples. Due to the rapid increase of gene discovery using high throughput DNA microarrays, TMAs have an excellent potential to authenticate the proteomic and genomic data across multiple types of tumor in a limited time. Diagnostic biomarkers can be utilized as a surrogate endpoint in clinical research, screening tool for diseases, or subclass identification of a disease.
b) Prognostic Biomarker Validation
For prognostic biomarker validation, TMAs are now used as the standard too for authentication. Specimen and sample banks have more data leading to the possibility of performing biomarker expression correlations with goals such as improving survival and prognosis. For example, it has been demonstrated that TMA has validated that a high expression of ezrin is linked with a poor prognosis and earlier metastasis. Another study has also observed that TROP2 overexpression is linked to lower prognosis of oral cavity squamous cell carcinoma.
c) Therapy Response
TMAs are increasingly used to define the possibility of developing specific therapeutic targets. It is constructed from patients who are receiving particular treatment methods. This means that TMA is a great tool to validate a predictive response to these treatments. This is now increasingly a popular method in research for translational cancer. It is also useful in TMA based studies that involve non-cancer pathology such as cardiac, dermatological, and placental diseases.
d) Clinical Applications
TMAs are also useful in pathology departments where new probes and antibodies are being tested. It is being utilized in clinical trials where pathological tissues are taken before the therapeutic trial starts. The TMA is used to determine the functional status of the cancer before therapy starts.
e) Quality Control
Quality control is one of the biggest issues in immunohistochemistry when it comes to diagnostic pathology. The high variations in laboratory results are mostly due to lab differences in the processes of staining protocols, antigen retrieval, the use of antibodies, and the interpretation of results. A study has shown that TMAs can now be used to enable individual pathology labs to perform their own quality control benchmarks.
f) Education and Tissue Repository
TMA is a valuable tool in the pooling of pathology specimens from pathology departments all across the nation. This enables it to be used for organization for education, facilitation of multicentric studies, and organization of long term specimen banking. There is so much data generated from TMA experiments on the database that collates all information that is related to TMA.
The main limitation of TMA was believed to be the potential that tissue cylinders might not be able to represent all sections especially tumors due to intratumor heterogeneity. Studies have reported that two cores from the same sample block gives equivalent information to that of whole sections. This means that this limitation can be resolved by increasing the cylinder or core diameter and number of cores.
Avninder S, Ylaya K, Hewitt SM. Tissue microarray: a simple technology that has revolutionized research in pathology. JPGM. 2008; 54(2): 158-162.