title: Development and validation of a gene expression tumour classifier for cancer of unknown primary.
abstract: Accurate identification of the primary tumour in cancer of unknown primary (CUP) is required for effective treatment selection and improved patient outcomes. The aim of this study was to develop and validate a gene expression tumour classifier and integrate it with histopathology to identify the likely site of origin in CUP.RNA was extracted from 450 formalin fixed, paraffin embedded samples of known origin comprising 18 tumour groups. Whole genome expression analysis was performed using a bead-based array. Classification of the tumours made use of a binary support vector machine, together with recursive feature elimination. A hierarchical tumour classifier was developed and incorporated with conventional histopathology to identify the origins of metastatic tumours.The classifier demonstrated an accuracy of 88% for correctly predicting the tumour type on a validation set of known tumours (n = 94). For CUP samples (n = 49) having a final clinical diagnosis, the classifier improved the accuracy of histology alone for both single and multiple predictions. Furthermore, where histology alone could not suggest any specific diagnosis, the classifier was able to correctly predict the primary site of origin.We demonstrate the integration of gene expression profiling with conventional histopathology to aid the investigation of CUP.
authors.affiliation: 1Peter MacCallum Cancer Centre, East Melbourne 2National (ICT) Australia, The University of Melbourne, Parkville 3Healthscope Pathology, Clayton 4Circadian Technologies Limited, Toorak 5The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville 6The Department of Pathology, University of Melbourne, Parkville 7The Department of Biochemistry, University of Melbourne, Parkville, Vic, Australia.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Tothill
authors.forename: Fan
authors.initials: F
authors.lastname: Shi
authors.forename: Lisa
authors.initials: L
authors.lastname: Paiman
authors.forename: Justin
authors.initials: J
authors.lastname: Bedo
authors.forename: Adam
authors.initials: A
authors.lastname: Kowalczyk
authors.forename: Linda
authors.initials: L
authors.lastname: Mileshkin
authors.forename: Evangeline
authors.initials: E
authors.lastname: Buela
authors.forename: Robert
authors.initials: R
authors.lastname: Klupacs
authors.forename: David
authors.initials: D
authors.lastname: Bowtell
authors.forename: Keith
authors.initials: K
authors.lastname: Byron
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000145:classification / Q000175:diagnosis* / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests
chemical_list: D014408:Biomarkers, Tumor