title: Prospective gene signature study using microRNA to identify the tissue of origin in patients with carcinoma of unknown primary.
abstract: OBJECTIVE
  Accurate identification of tissue of origin (ToO) for patients with carcinoma of unknown primary (CUP) may help customize therapy to the putative primary and thereby improve the clinical outcome. We prospectively studied the performance of a microRNA-based assay to identify the ToO in CUP patients.
  
  
  METHODS
  Formalin-fixed paraffin-embedded (FFPE) metastatic tissue from 104 patients was reviewed and 87 of these contained sufficient tumor for testing. The assay quantitates 48 microRNAs and assigns one of 25 tumor diagnoses by using a biologically motivated binary decision tree and a K-nearest neighbors (KNN). The assay predictions were compared with clinicopathologic features and, where suitable, to therapeutic response.
  
  
  RESULTS
  Seventy-four of the 87 cases were processed successfully. The assay result was consistent or compatible with the clinicopathologic features in 84% of cases processed successfully (71% of all samples attempted). In 65 patients, pathology and immunohistochemistry (IHC) suggested a diagnosis or (more often) a differential diagnosis. Out of those, the assay was consistent or compatible with the clinicopathologic presentation in 55 (85%) cases. Of the 9 patients with noncontributory IHC, the assay provided a ToO prediction that was compatible with the clinical presentation in 7 cases.
  
  
  CONCLUSIONS
  In this prospective study, the microRNA diagnosis was compatible with the clinicopathologic picture in the majority of cases. Comparative effectiveness research trials evaluating the added benefit of molecular profiling in appropriate CUP subsets are warranted. MicroRNA profiling may be particularly helpful in patients in whom the IHC profile of the metastasis is nondiagnostic or leaves a large differential diagnosis.
authors.affiliation: Departments of Gastrointestinal Medical Oncology and Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Gauri R
authors.initials: GR
authors.lastname: Varadhachary
authors.forename: Yael
authors.initials: Y
authors.lastname: Spector
authors.forename: James L
authors.initials: JL
authors.lastname: Abbruzzese
authors.forename: Shai
authors.initials: S
authors.lastname: Rosenwald
authors.forename: Huamin
authors.initials: H
authors.lastname: Wang
authors.forename: Ranit
authors.initials: R
authors.lastname: Aharonov
authors.forename: Heather R
authors.initials: HR
authors.lastname: Carlson
authors.forename: Dalia
authors.initials: D
authors.lastname: Cohen
authors.forename: Siddharth
authors.initials: S
authors.lastname: Karanth
authors.forename: Joanna
authors.initials: J
authors.lastname: Macinskas
authors.forename: Renato
authors.initials: R
authors.lastname: Lenzi
authors.forename: Ayelet
authors.initials: A
authors.lastname: Chajut
authors.forename: Tina B
authors.initials: TB
authors.lastname: Edmonston
authors.forename: Martin N
authors.initials: MN
authors.lastname: Raber
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics / Q000556:secondary*; D003663:Decision Trees; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D011446:Prospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D035683:MicroRNAs