The tissue micro-array as a translational research tool for biomarker profiling and validation.

Abstract

High-throughput molecular technologies have provided a wealth of putative biomarkers representing potential diagnostic, prognostic and therapeutic targets. Target validation commonly requires abundant and well-characterized tissue resources, as well as linked clinicopathologic data-sets. The tissue micro-array (TMA) is a validation and discovery platform of increasing popularity and necessity. TMAs provide a rapid means of examining in situ gene expression in a wide spectrum and large number of tissue samples. This paper describes the uses of TMAs as a translational research tool in biomarker profiling. The laboratory has performed numerous biomarker studies on several types of epithelial cancers. As an example, Epithelial Protein Cell Adhesion Molecule (EpCAM), a panepithelial antigen used to target tumours with immunotherapy, was examined in patients with renal cell carcinoma (RCC). EpCAM was an independent prognosticator for improved disease-specific survival in 318 clear cell RCCs examined, with a Cox proportional hazards multivariate hazard ratio of 0.63 (p=0.017; 95% confidence interval 0.43-0.92). Interestingly, despite a typically widespread epithelial expression, EpCAM is instead infrequently expressed in clear cell RCC, the most common type of renal cancer, making it a poor target for immunotherapy. In this capacity the TMA provided strong support for halting lengthy and costly clinical trials for this application.