title: A quantitative reverse transcriptase-polymerase chain reaction assay to identify metastatic carcinoma tissue of origin.
abstract: Identifying the primary site in patients with metastatic carcinoma of unknown primary origin can enable more specific therapeutic regimens and may prolong survival. Twenty-three putative tissue-specific markers for lung, colon, pancreatic, breast, prostate, and ovarian carcinomas were nominated by querying a gene expression profile database and by performing a literature search. Ten of these marker candidates were then selected based on validation by reverse transcriptase-polymerase chain reaction (RT-PCR) on 205 formalin-fixed, paraffin-embedded metastatic carcinoma specimens originating from these six and from other cancer types. Next, we optimized the RNA isolation and quantitative RT-PCR methods for these 10 markers and applied the quantitative RT-PCR assay to a set of 260 metastatic tumors. We then built a gene-based algorithm that predicted the tissue of origin of metastatic carcinomas with an overall leave-one-out cross-validation accuracy of 78%. Lastly, our assay demonstrated an accuracy of 76% when tested on an independent set of 48 metastatic samples, 37 of which were either a known primary or initially presented as carcinoma of unknown primary but were subsequently resolved.
authors.affiliation: Veridex LLC, 33 Technology Dr., Warren, NJ 07059, USA.
authors.forename: Dimitri
authors.initials: D
authors.lastname: Talantov
authors.forename: Jonathan
authors.initials: J
authors.lastname: Baden
authors.forename: Tim
authors.initials: T
authors.lastname: Jatkoe
authors.forename: Kristina
authors.initials: K
authors.lastname: Hahn
authors.forename: Jack
authors.initials: J
authors.lastname: Yu
authors.forename: Yashoda
authors.initials: Y
authors.lastname: Rajpurohit
authors.forename: Yiqiu
authors.initials: Y
authors.lastname: Jiang
authors.forename: Chang
authors.initials: C
authors.lastname: Choi
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Ross
authors.forename: David
authors.initials: D
authors.lastname: Atkins
authors.forename: Yixin
authors.initials: Y
authors.lastname: Wang
authors.forename: Abhijit
authors.initials: A
authors.lastname: Mazumder
mesh_terms: D000465:Algorithms; D014408:Biomarkers, Tumor / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D009362:Neoplasm Metastasis / Q000235:genetics*; D009382:Neoplasms, Unknown Primary / Q000175:diagnosis* / Q000235:genetics*; D016612:Paraffin Embedding; D011237:Predictive Value of Tests; D040081:Protein Array Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods*
chemical_list: D014408:Biomarkers, Tumor