Interlaboratory performance of a microarray-based gene expression test to determine tissue of origin in poorly differentiated and undifferentiated cancers.
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 kappa statistics (kappa >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.
Dumur
Catherine I
CI
Department of Pathology, Virginia Commonwealth University, Richmond, Virginia, USA.
Lyons-Weiler
Maureen
M
Sciulli
Christin
C
Garrett
Carleton T
CT
Schrijver
Iris
I
Holley
Tara K
TK
Rodriguez-Paris
Juan
J
Pollack
Jonathan R
JR
Zehnder
James L
JL
Price
Melissa
M
Hagenkord
Jill M
JM
Rigl
C Ted
CT
Buturovic
Ljubomir J
LJ
Anderson
Glenda G
GG
Monzon
Federico A
FA
D006801:Humans; D009369:Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods* / Q000592:standards*; D012334:RNA, Neoplasm / Q000235:genetics; D015203:Reproducibility of Results
D012334:RNA, Neoplasm