Validation of a Gene Expression Test for Mesothelioma Prognosis in Formalin-Fixed Paraffin-Embedded Tissues

J Mol Diagn. 2017 Jan;19(1):65-71. doi: 10.1016/j.jmoldx.2016.07.011. Epub 2016 Nov 15.

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.

Publication types

  • Validation Study

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Female
  • Formaldehyde
  • Gene Expression Profiling / methods*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Mesothelioma / diagnosis
  • Mesothelioma / genetics
  • Mesothelioma / metabolism*
  • Mesothelioma / mortality
  • Middle Aged
  • Multivariate Analysis
  • Paraffin Embedding
  • Pleural Neoplasms / diagnosis
  • Pleural Neoplasms / genetics
  • Pleural Neoplasms / metabolism*
  • Pleural Neoplasms / mortality
  • Prognosis
  • Proportional Hazards Models
  • Tissue Fixation
  • Transcriptome

Substances

  • Biomarkers, Tumor
  • Formaldehyde