title: Validation of a Gene Expression Test for Mesothelioma Prognosis in Formalin-Fixed Paraffin-Embedded Tissues.
abstract: A molecular test performed using fresh-frozen tissue was proposed for use in the prognosis of patients with pleural mesothelioma. The accuracy of the test and its properties was assessed under Clinical Laboratory Improvement Amendments-approved guidelines using FFPE tissue from an independent multicenter patient cohort. Concordance studies were performed using matched frozen and FFPE mesothelioma samples. The prognostic value of the test was evaluated in an independent validation cohort of 73 mesothelioma patients who underwent surgical resection. FFPE-based classification demonstrated overall high concordance (83%) with the matched frozen specimens, on removal of cases with low confidence scores, showing sensitivity and specificity in predicting type B classification (poor outcome) of 43% and 98%, respectively. Concordance between research and clinical methods increased to 87% on removal of low confidence cases. Median survival times in the validation cohort were 18 and 7 months in type A and type B cases, respectively (P = 0.002). Multivariate classification adding pathologic staging information to the gene expression score resulted in significant stratification of risk groups. The median survival times were 52 and 14 months in the low-risk (class 1) and intermediate-risk (class 2) groups, respectively. The prognostic molecular test for mesothelioma can be performed on FFPE tissues to predict survival, and can provide an orthogonal tool, in combination with established pathologic parameters, for risk evaluation.
authors.affiliation: Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program, Division of Thoracic Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Assunta
authors.initials: A
authors.lastname: De Rienzo
authors.affiliation: Castle Biosciences, Inc., Friendswood, Texas.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Cook
authors.affiliation: DNA Diagnostics Laboratory, St. Joseph's Hospital and Medical Center, Phoenix, Arizona.
authors.forename: Jeff
authors.initials: J
authors.lastname: Wilkinson
authors.affiliation: Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program, Division of Thoracic Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Corinne E
authors.initials: CE
authors.lastname: Gustafson
authors.affiliation: National Mesothelioma Virtual Bank, Pittsburgh, Pennsylvania; Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Waqas
authors.initials: W
authors.lastname: Amin
authors.affiliation: Castle Biosciences, Inc., Friendswood, Texas.
authors.forename: Clare E
authors.initials: CE
authors.lastname: Johnson
authors.affiliation: Castle Biosciences, Inc., Friendswood, Texas.
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Oelschlager
authors.affiliation: Castle Biosciences, Inc., Friendswood, Texas.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Maetzold
authors.affiliation: DNA Diagnostics Laboratory, St. Joseph's Hospital and Medical Center, Phoenix, Arizona.
authors.forename: John F
authors.initials: JF
authors.lastname: Stone
authors.affiliation: National Mesothelioma Virtual Bank, Pittsburgh, Pennsylvania; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Feldman
authors.affiliation: National Mesothelioma Virtual Bank, Pittsburgh, Pennsylvania; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Becich
authors.affiliation: Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Beow Y
authors.initials: BY
authors.lastname: Yeap
authors.affiliation: Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program, Division of Thoracic Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: William G
authors.initials: WG
authors.lastname: Richards
authors.affiliation: Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program, Division of Thoracic Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: rbueno@partners.org.
authors.forename: Raphael
authors.initials: R
authors.lastname: Bueno
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D005260:Female; D005557:Formaldehyde; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008654:Mesothelioma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D008875:Middle Aged; D015999:Multivariate Analysis; D016612:Paraffin Embedding; D010997:Pleural Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D011379:Prognosis; D016016:Proportional Hazards Models; D016707:Tissue Fixation; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; D005557:Formaldehyde