Effects of Tissue Handling on RNA Integrity and Microarray

Genomic profiling has enabled the identification of molecular subclasses of tumors that are associated with different prognostic outcomes (1) or differential response to breast cancer treatments (2–4). Such multiplex molecular assays could support personalized cancer treatment (5,6). Indeed, multigene predictive or prognostic tests based on measurements of RNA expression—some of which use a microarray platform (7)—are now offered commercially. In addition, microarray-based genomic data are widely used by cancer researchers. However, information about how the biological samples were collected and preserved is usually limited in research tissue cohorts. Therefore, to inform best practices for sample col-lection in clinical research and practice, it is important to evaluate systematically variables of biospecimen integrity that affect the quality of isolated RNA and expression measurements of single genes and multigene signatures (8–10). There are two main sources of variability in gene expression measurements: pre-analytic sources, which are related to the tumor sample itself and influenced by the sample collection process, and technical sources, which are related to the analytical platform. The Food and Drug Administration–sponsored MicroArray Quality Control Consortium assessment of the analytical performance of several quantitative gene expression platforms con-firmed agreement in gene expression measurements generated by different commercial microarray platforms (11) and by quantitativ