title: Implementation of a novel microarray-based diagnostic test for cancer of unknown primary.
abstract: 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.
authors.affiliation: Agendia BV, SciencePark 406, 1098 XH Amsterdam, The Netherlands.
authors.forename: Ryan K
authors.initials: RK
authors.lastname: van Laar
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Ma
authors.forename: Daphne
authors.initials: D
authors.lastname: de Jong
authors.forename: Diederik
authors.initials: D
authors.lastname: Wehkamp
authors.forename: Arno N
authors.initials: AN
authors.lastname: Floore
authors.forename: Marc O
authors.initials: MO
authors.lastname: Warmoes
authors.forename: Iris
authors.initials: I
authors.lastname: Simon
authors.forename: Wilson
authors.initials: W
authors.lastname: Wang
authors.forename: Mark
authors.initials: M
authors.lastname: Erlander
authors.forename: Laura J
authors.initials: LJ
authors.lastname: van't Veer
authors.forename: Annuska M
authors.initials: AM
authors.lastname: Glas
mesh_terms: 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