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

Abstract

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. (J Mol

Occult Primary, Version 3.2014

“…Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine; 11 Huntsman Cancer Institute at the University of Utah; 12 University of Alabama at Birmingham Comprehensive Cancer Center; 13 Roswell Park Cancer Institute; 14 The University of Texas MD Anderson Cancer Center; 15 The Ohio State University Comprehensive Cancer Center -James Cancer Hospital and Solove Research Institute; 16 Memorial Sloan Kettering Cancer Center; 17 UC San Diego Moores Cancer Center; 18 Dana-Farber/Brigham and Women's Cancer Center; 19 University of Michigan Comprehensive Cancer Center; 20 Duke Cancer Institute; 21 Moffitt Cancer Center; 22 Fred & Pamela Buffett Cancer Center at The Nebraska Medical Center; and 23 National Comprehensive Cancer Network.…”

Pan-cancer transcriptome analysis reveals a gene expression signature for the identification of tumor tissue origin

“…46 Indeed, pancreatic cancer is the most difficult type of carcinoma of unknown primary to identify using our method as well as all published methods. 8,24,[47][48][49][50] Additional research is needed to successfully translate the 154-gene signature from gene expression microarray to real-time reverse transcription polymerase chain reaction assays, thus allowing broader access and utilization in the clinical setting. In routine practice, most diagnostic materials are formalin-fixed and paraffin-embedded; thus, it will be highly interesting to assess the usefulness of the 154-gene signature in formalin-fixed and paraffin-embedded samples.…”

Cost-effectiveness of using a gene expression profiling test to aid in identifying the primary tumour in patients with cancer of unknown primary

“…2 In the past decade, improvements in the number and accuracy of IHC stains have enabled pathologists and oncologists to make highly accurate tissue-of-origin diagnosis in many of these metastatic patients. 3,4 However, the current success rate of the diagnostic work-up, even after exhaustive clinical and pathologic investigation, varies from 20 to 25%. 3,4 Consequently, about 5000 new cancer cases are annually diagnosed with cancer of unknown primary (CUP) in Canada.…”

“…9,10 To date, several gene expression-based tests have demonstrated the potential value of this approach in identifying the primary site. 4,[11][12][13][14][15][16][17][18][19][20][21][22][23][24] One microarray-based test uses 2000-GEP to identify a tumour's primary site using formalin-fixed paraffin-embedded (FFPE) specimens (Tissue of Origin test, Response Genetics, Inc., Los Angeles, CA). 24 The test compares the RNA profile of a tumour FFPE specimen to established RNA profiles of 15 known tissues.…”