Tissue Microarrays in Clinical Oncology
Section snippets
TMA Construction and Analysis
The initial identification and collection of tumor samples represents the greatest portion of the work associated with TMA construction. Samples need to be identified based on their availability in sufficient numbers to address the proposed scientific or clinical question. For example, prognostic studies will require a large number of cases with long-term outcome data to provide adequate statistical power. Similarly, a study investigating a novel diagnostic biomarker may require the
Advantages of TMAs
The staining of a few TMA sections in comparison to many more whole sections offers a clear benefit with respect to the use of laboratory reagents and technician time. Because several research groups are now using TMAs representing in excess of 1,000 tumors, this approach represents a major savings in scientific resources. In addition, there is also the benefit of decreased technical variability during the staining and interpretation process. The close proximity of cores also permits more rapid
TMAs in the Study of Tumor Biology
TMAs permit the rapid assessment of individual molecular markers on large patient cohorts. This approach complements molecular screening and discovery studies by confirming results on large numbers of primary tumor cases. TMAs have been so used in the initial articles characterizing new breast cancer oncogenes such as EMSY3 and alpha-basic crystallin4 and the recently identified prostate cancer fusion oncogene TMPRSS2:ERG.5
TMAs are similarly useful in characterizing the immunohistochemical
TMAs for the Assessment of New Diagnostic Tools
In modern oncology, treatment decisions are critically dependent on accurate diagnostic pathology. Increasingly, molecular biomarkers are used in conjunction with conventional histology to improve diagnostic accuracy. Examples include the use of cytokeratin stain to localize micrometastases in sentinel lymph node biopsies for breast cancer and the use of antibody panels to ascertain a tissue diagnosis for a metastasis of unknown primary origin. Primary unknown malignancies are particularly
TMAs for the Assessment of Prognostic and Predictive Values
In the clinical practice of oncology, therapeutic decisions regarding adjuvant treatment are often based on a clinician’s estimate of recurrence risk and the expected therapeutic gain from a specific treatment. More recently, clinicians have at their disposal prognostic models that are based on the retrospective analysis of large outcome databases. Examples include the Kattan nomograms for prostate cancer,21 and the Web-based prediction tool “Adjuvant! Online” for breast and colorectal
TMAs in Quality Control and Clinical Practice
Although TMA studies are an important tool for the validation of novel biomarkers, most molecular epidemiology studies are derived from a single institution, and even if the tumor samples are collected from multiple sites, sample processing and data collection and analysis are performed centrally. There are multiple reports in the medical literature of conflicting results on the prognostic or predictive value of a novel biomarker. One example is cyclin E in breast cancer, for which 1 research
Validation of TMA Analysis
The most frequent criticism of TMA technology relates to the small size of each tissue core; there is concern that because of tumor heterogeneity, biomarker scores obtained from small TMA cores will not accurately reflect scores obtained from whole sections.43, 51, 52 However, it should be noted that although whole-section analysis is a “gold standard” for in situ tests, whole sections themselves represent just a small portion of a tumor, and, indeed core needle, punch, and bite biopsies used
Conclusion and Future Directions
The most important step in initiating a TMA study is the identification of appropriate patient cohorts with accessible archival tissue materials. Prognostic studies require patient data that are thorough and complete and include long-term follow-up. Diagnostic studies may require locating source blocks from multiple tumor types and tissues in various stages of malignant progression.
In laboratory medicine, TMAs already play an important role in quality assurance and the characterization of new
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David Voduc and Torsten O. Nielsen are supported by the National Institutes of Health Strategic Partnering to Evaluate Cancer Signatures program. Torsten O. Nielsen is a scholar of the Michael Smith Foundation for Health Research. The Genetic Pathology Evaluation Centre is supported by an unrestricted educational grant from sanofi-aventis.