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 Amendmentseapproved 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 Z 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.

Should the surgical decision be influenced by the diagnostic biopsy in mesothelioma?

“…The test demonstrates high repeatability and reproducibility, successfully discriminating high and low risk patients based on outcomes following surgery-based therapy. Importantly, the test was further validated using formalin-fixed paraffinembedded tissue samples, which supports its applicability to routinely collected clinical material (24). In addition, recent RNA-Seq profiling of over two hundred MPM tumors led to identification of distinct molecular clusters that align approximately with tumor histology, reflect gene expression signatures indicative of epithelial to mesenchymal transition and stratify survival (25).…”

Whole transcriptome targeted gene quantification provides new insights on pulmonary sarcomatoid carcinomas

“…To analyse gene expression profiles of our samples, we used a targeted whole transcriptome sequencing approach reported as highly accurate and perfectly comparable with RNA-sequencing approaches and next generation sequencing platforms utilized to obtain TCGA data 16 . Although TCGA samples are fresh frozen and we analysed only formalin-fixed and paraffin-embedded (FFPE) tissues, the comparison of transcriptome data is supported by several evidences demonstrating a high correlation of gene expression profiles between these two types of specimens 17–19 . Anyway, in order to overcome this potential limitation, a validation of results was carried out on an independent cohort of PSC, LUAD and LUSC FFPE tissues from our archives.…”

Intensity‐modulated radiotherapy is a safe and effective treatment for localized malignant pleural mesothelioma

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