Published online before print December 13, 2007

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Journal of Molecular Diagnostics 2008, Vol. 10, No. 1
Copyright © 2008 American Society for Investigative Pathology & Association for Molecular Pathology
DOI: 10.2353/jmoldx.2008.070099

Interlaboratory Performance of a Microarray-Based Gene Expression Test to Determine Tissue of Origin in Poorly Differentiated and Undifferentiated Cancers

Catherine I. Dumur^*, Maureen Lyons-Weiler, Christin Sciulli, Carleton T. Garrett^*, Iris Schrijver, Tara K. Holley^*, Juan Rodriguez-Paris, Jonathan R. Pollack, James L. Zehnder, Melissa Price, Jill M. Hagenkord, C. Ted Rigl, Ljubomir J. Buturovic, Glenda G. Anderson and Federico A. Monzon

From the Department of Pathology, *Virginia Commonwealth University, Richmond, Virginia; the Clinical Genomics Facility and Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania; the Department of Pathology, Stanford University, Stanford, California; and Pathwork Diagnostics, Sunnyvale, California

Clinical workup of metastatic malignancies of unknown origin is often arduous and expensive and is reported to be unsuccessful in 30 to 60% of cases. Accurate classification of uncertain primary cancers may improve with microarray-based gene expression testing. We evaluated the analytical performance characteristics of the Pathwork tissue of origin test, which uses expression signals from 1668 probe sets in a gene expression microarray, to quantify the similarity of tumor specimens to 15 known tissues of origin. Sixty archived tissue specimens from poorly and undifferentiated tumors (metastatic and primary) were analyzed at four laboratories representing a wide range of preanalytical conditions (eg, personnel, reagents, instrumentation, and protocols). Cross-laboratory comparisons showed highly reproducible results between laboratories, with correlation coefficients between 0.95 to 0.97 for measurements of similarity scores, and an average 93.8% overall concordance between laboratories in terms of final tissue calls. Bland-Altman plots (mean coefficients of reproducibility of 32.48 ± 3.97) and statistics ( > 0.86) also indicated a high level of agreement between laboratories. We conclude that the Pathwork tissue of origin test is a robust assay that produces consistent results in diverse laboratory conditions reflecting the preanalytical variations found in the everyday clinical practice of molecular diagnostics laboratories.

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