title: Accurate classification of metastatic brain tumors using a novel microRNA-based test.
abstract: BACKGROUND
  Identification of the tissue of origin of a brain metastatic tumor is vital to its management. Carcinoma of unknown primary (CUP) is common in oncology, representing 3%-5% of all invasive malignancies. We aimed to validate a recently developed microRNA-based quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) test for identifying the tumor tissue of origin, first in a consecutive cohort of metastatic tumors of known origin and then in a cohort of CUP cases resected from the central nervous system (CNS).
  
  
  METHODS
  One hundred two resected CNS metastatic tumors with known origin, previously classified based on the patient's clinical history and pathological data, as well as a second cohort of resected CNS tumors from 57 patients originally diagnosed as CUP were studied. A qRT-PCR diagnostic assay that measures the expression level of 48 microRNAs was used to classify the tissue of origin of these metastatic tumors.
  
  
  RESULTS
  In this blinded study, the test predictions correctly identified the reference diagnosis of the samples of known origin, excluding samples from prostate origin, in 84% of cases. In the second CUP patient cohort, the test prediction was in agreement with the diagnosis that was later confirmed clinically or with pathological evaluation in 80% of cases.
  
  
  CONCLUSIONS
  In a cohort of brain and spinal metastases, a previously developed test based on the expression of 48 microRNAs allowed accurate identification of the tumor tissue of origin in the majority of cases. The high accuracy of this test in identifying the tissue of origin of metastases of unknown primary is demonstrated for the first time and may have broad clinical application.
authors.affiliation: Department of Neuropathology, Institute of Pathology, Ruprecht-Karls University Heidelberg, 69120 Heidelberg INF 220, Germany. wolf.mueller@med.uni-heidelberg.de
authors.forename: Wolf C
authors.initials: WC
authors.lastname: Mueller
authors.forename: Yael
authors.initials: Y
authors.lastname: Spector
authors.forename: Tina Bocker
authors.initials: TB
authors.lastname: Edmonston
authors.forename: Brianna
authors.initials: B
authors.lastname: St Cyr
authors.forename: Diana
authors.initials: D
authors.lastname: Jaeger
authors.forename: Ulrike
authors.initials: U
authors.lastname: Lass
authors.forename: Ranit
authors.initials: R
authors.lastname: Aharonov
authors.forename: Shai
authors.initials: S
authors.lastname: Rosenwald
authors.forename: Ayelet
authors.initials: A
authors.lastname: Chajut
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D001932:Brain Neoplasms / Q000145:classification* / Q000235:genetics / Q000556:secondary*; D016543:Central Nervous System Neoplasms / Q000556:secondary; D015331:Cohort Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D035683:MicroRNAs / Q000032:analysis*; D009382:Neoplasms, Unknown Primary / Q000175:diagnosis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011237:Predictive Value of Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods / Q000592:standards*; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs