Tissue Microarrays: A Current Medical Research Tool

Iqbal S. Shergill; N. K. Shergill; M. Arya; H. R. H. Patel


Curr Med Res Opin. 2004;20(5) 

In This Article

Morphological and Molecular Analysis of TMAs

At the present time, 80% of TMAs produced are analysed using immunohistochemistry, whereas most of the remaining TMAs are being investigated by in situ hybridisation techniques, such as interphase FISH.[11] In addition, recent reports have been published on frozen tissue[12] and cell lines.[13]

The use of TMAs has significant advantages over standard techniques. TMAs allow the simultaneous analysis of very large numbers of specimens, allowing high throughput data acquisition. For example, if a TMA block containing 1000 cores is cut 200 times, as many as 200 000 individual assays, and therefore outcomes can be produced from a single block.[14,15] Furthermore, as all the tissue specimens arrayed on one TMA are analysed in an identical fashion, antigen retrieval, reagent concentrations, incubation times with primary antibodies, temperatures and wash conditions are identical for each core,[16] resulting in an unprecedented level of standardization, over and above what is available using standard histopathological techniques. In addition, as only small quantities of reagent, and less laboratory personnel are required to perform the experiments, this method has proven to be extremely efficient and cost effective. The histopathological benefits include minimal destruction of the original tissue blocks, which are often considered as vital resources, the presence of internal positive and negative controls on the TMA, and because such small specimens are sampled, many rare cell lines can be assessed with ease.[13]

One potential limitation of TMAs is that the small cores sampled may not be representative of whole tumours, particularly in heterogenous cancers such as prostate adenocarcinoma. This issue has been critically evaluated in studies where TMAs have been compared with whole mount sections. Excellent correlation has been reported between data obtained from the two techniques in a variety of tumour types such as breast,[17] prostate,[18,19] bladder[20] and human fibroblastic tumours.[21] Furthermore, in the most extensive study investigating this issue of validation in prostate cancer Rubin et al., found that 3-4 cores were the optimal number necessary to predict outcome after radical prostatectomy for localised prostate cancer.[18] Similarly, other groups have found that sampling with optimal cores was sufficient to accurately detect clinicopathological correlations.[19,21,22] Interestingly, these studies have shown that increasing the number of cores, to compensate for heterogeneity and inevitable losses, only confers a slightly higher rate of validity, with the significant disadvantages of additional labour work in arraying a larger number of arrays and lack of efficiency in processing of tissues.