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

Applications of TMAs

Genes identified by DNA microarray studies require clinical validation on histopathological specimens for any meaningful outcome. TMAs are ideally suited for this purpose and most published studies using TMAs have reported on this application, allowing the identification of clinically relevant diagnostic and prognostic markers. Interestingly, the majority of these reports have been related to the analysis of tumour specimens. Depending on the type of tissue sampled and the clinical follow-up available, three categories of TMA can be defined.

Many tumour types are sampled, from a diverse set of donor blocks, and arrayed on one recipient TMA block. With this type of TMA, a large group of tumours can then be expeditiously screened for the presence or absence of novel markers.[23,24,25]

Morphological and molecular changes through the different stages of tumour progression, of one particular tumour type, can be assessed in tumour progression TMAs. In prostate cancer, for example, construction of such an array would involve sampling of normal prostate, benign prostatic hyperplasia, prostatic intraepithelial neoplasia and different stages of prostate cancer, from localised disease to metastatic cancer. In one of the most significant papers on prostate cancer recently, a tumour progression array was used to show that the expression of a novel protein, EZH2, correlated with aggressiveness of disease.[26] Similar studies have been published on breast cancer.[27]

Whilst multi-tumour arrays and progression arrays provide useful diagnostic information, correlation of TMA derived data with clinical follow-up, to assess prognosis or patient outcome, is of significant interest to clinicians and their patients. One such example is the study involving the EZH2 protein.[26] In addition to its use as a marker of prostate cancer progression, Varambally et al., showed that the degree of expression of this protein was related to outcome after radical prostatectomy. Whilst strong expression was associated with recurrence of tumour after surgery in a third of patients, weak EZH2 staining was found in only 9% of individuals with clinical failure. Similar associations with prognosis have also been described in neoplasms of the breast,[27] bladder[28] and kidney[29] using patient outcome arrays.

Recently, it has been suggested that combinations of expression of novel markers may be of more benefit in predicting prognosis.[30] Rhodes et al. investigated 14 candidate prognostic markers in prostate cancer, including hepsin, AMACR, E-Cadherin and EZH2. They found that only the ratio of EZH2 to E-Cadherin staining was statistically associated with prostate cancer recurrence following radical prostatectomy. This approach may be useful in identifying patients who are at high risk of recurrence and therefore providing them with alternative and appropriate treatment. As TMAs incorporate a high throughput approach, they are very well suited for this 'multiplex biomarker approach'.