Implementation of a novel microarray-based diagnostic test for cancer of unknown primary.
Patients with carcinoma of unknown primary (CUP) present with metastatic disease for which the primary site cannot be found, despite extensive standard investigation. Here, we describe the development and implementation of the first clinically available microarray-based test for this cancer type (CUPPrint), based on 633 individual tumors representing 30 carcinoma and 17 noncarcinoma classes. Tissue of origin prediction for either fresh frozen or paraffin-embedded tumor samples is achieved with the use of a custom 8-pack 1.9k microarray and robust classification algorithm. An expression profile of 495 genes was used to predict tumor origin by applying a k-nearest neighbor algorithm. Internal cross-validation and analysis of an independent, previously published, 229-sample dataset revealed that clinically informative predictions were made for up to 94% of samples analyzed. Analysis of 13 previously published CUP specimens yielded predicted tumor origins that supported the clinical suspicion in 12 cases (92%). Microarray profiling presents a promising tool to assist in the identification of the primary tumor and might direct a more tailored treatment for CUP patients.
van Laar
Ryan K
RK
Agendia BV, SciencePark 406, 1098 XH Amsterdam, The Netherlands.
Ma
Xiao-Jun
XJ
de Jong
Daphne
D
Wehkamp
Diederik
D
Floore
Arno N
AN
Warmoes
Marc O
MO
Simon
Iris
I
Wang
Wilson
W
Erlander
Mark
M
van't Veer
Laura J
LJ
Glas
Annuska M
AM
D000465:Algorithms; D002454:Cell Differentiation; D003955:Diagnostic Tests, Routine; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009367:Neoplasm Staging; D009382:Neoplasms, Unknown Primary / Q000145:classification / Q000175:diagnosis* / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D016612:Paraffin Embedding; D011379:Prognosis