Histopathological typing in diffuse malignant epithelioid mesothelioma: implication for prognosis and molecular basis

Our plain-English summary of Histopathological typing in diffuse malignant epithelioid mesothelioma: implication for prognosis and molecular basis, by F. Forest, D. Laville, C. Habougit, et al (Pathology, 2021).

The study

• Authors: F. Forest, D. Laville, C. Habougit, M. Corbasson, S. Bayle-Bleuez, C. Tissot, P. Fournel, O. Tiffet, M. Péoc'h
• Journal: Pathology
• Published: 2021;53(6):728-734
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The prognostic impact of tumour grading, cytological and architectural patterns and stromal features in diffuse pleural malignant epithelioid mesothelioma (MEM) has been partly studied but not correlated to molecular features. We performed a retrospective study on 92 MEM in our department in order to assess the prognostic role of architectural and stromal patterns, especially tumour to stroma ratio. Secondly, based on The Cancer Genome Atlas (TCGA) database, we analysed the differentially expressed genes in prognostic groups of interest. Our results showed that tumour grading, tumour to stroma ratio and predominant pattern were related to overall survival, p≤0.001, p=0.01 and p=0.001, respectively. In univariate analysis, for high grade tumours hazard ratio (HR) was 4.75 (2.47-9.16), for stroma poor tumours HR=0.016, for predominant tubular or tubulopapillary pattern HR=0.044. In multivariate analysis, high grade tumours were related to overall survival [HR=3.09 (1.50-6.35), p=0.002] and predominant tubular or tubulopapillary pattern [HR=0.56 (0.32-0.99), p=0.045]. In TCGA analysis, after grading of diagnostic slides, we showed that KRTDAP and CXRCR1 expression was higher in low grade tumours, unlike PDZD7 and GPR176 expression which was higher in high grade tumours. FAM81B had a higher expression in stroma poor tumours. We did not find any differentially expressed genes in the architectural patterns group. Our work suggests that tumour grading is an important parameter in MEM with an underlying genomic basis. The role of tumour to stroma ratio needs to be investigated and might also have a genomic basis.

Copyright © 2021 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

In plain English

This retrospective study came from one hospital pathology department in Saint Etienne, France. It looked at whether features seen under the microscope were linked to survival in 92 patients diagnosed from 2000 to 2020 with epithelioid mesothelioma of the pleura. The article does not report on asbestos exposure. The 72 patients with low grade tumours had a median overall survival of 24.2 months, compared with 10.1 months for the 20 with high grade tumours. Tumours with more stroma (supporting tissue) and tumours with a mainly tubular or tubulopapillary growth pattern were also linked to longer survival. When these features were analysed together, two remained linked to survival: high grade (hazard ratio 3.09, 95% confidence interval 1.50 to 6.35, where above 1 means a higher risk of death) and the tubular or tubulopapillary pattern (hazard ratio 0.56, 0.32 to 0.99). The amount of stroma did not. Using slides and genetic data on 51 epithelioid mesotheliomas from The Cancer Genome Atlas, the authors found four genes expressed differently by grade and one by stroma amount. The authors concluded that grading has a major prognostic role and might reflect the tumours' molecular status. They noted their small numbers as a limitation.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Single-centre (monocentric) retrospective study of pathology slides and survival, plus an analysis of tumour slides and molecular data from The Cancer Genome Atlas (TCGA) database
• Who was studied: 120 patients diagnosed with pleural mesothelioma at the University Hospital of Saint Etienne, France, from 2000 to 2020. Of these, 92 had epithelioid mesothelioma (70 males, 22 females, mean age 73.9 years), and these 92 were the main study group. A further 51 epithelioid mesothelioma cases were taken from the TCGA database.
• Main results:
  • Among the 92 epithelioid mesotheliomas, 72 were low grade and 20 high grade. Median overall survival was 24.2 months for low grade and 10.1 months for high grade (p less than 0.001).
  • Median overall survival was 27.2 months for stroma rich tumours and 14.8 months for stroma poor tumours (p=0.01).
  • By main growth pattern, median overall survival was 12 months for solid, 25.1 months for tubular or tubulopapillary, and 22.8 months for the other patterns (p=0.001).
  • Myxoid stroma, tertiary lymphoid structures and stromal vacuolisation were not associated with median overall survival.
  • In univariate Cox analysis, high grade had a hazard ratio of 4.75 (95% CI 2.47 to 9.16, p less than 0.001), stroma poor 1.89 (1.12 to 3.17, p=0.016), and tubular or tubulopapillary pattern 0.47 (0.23 to 0.98, p=0.044).
  • In multivariate Cox analysis, high grade had a hazard ratio of 3.09 (95% CI 1.50 to 6.35, p=0.002) and the tubular or tubulopapillary pattern 0.56 (0.32 to 0.99, p=0.045). Stroma poor (1.43, 0.82 to 2.49, p=0.20) was not significant.
  • In the TCGA cases, KRTDAP and CXCR1 were more expressed in low grade tumours, and PDZD7 and GPR176 in high grade tumours. There were no differences by grade in mutations or copy number alterations.
  • In the TCGA cases, FAM81B was more expressed in stroma poor tumours. No molecular differences were found between growth pattern groups.
  • Agreement between the two pathologists on grading (Cohen's kappa) was 0.71 in the hospital cases. 61 of the 92 tumours did not fit any of the predefined cytological categories.
• The authors' conclusion: The authors concluded that tumour grading has a major prognostic role in epithelioid mesothelioma and might reflect the molecular status of tumour cells. They found tumour to stroma ratio to be a prognostic factor in their work, but said it needs study in larger cohorts. They found predominant pattern to be a prognostic factor, with an unclear molecular basis.
• Limitations the authors state:
  • The study was based at a single centre, was retrospective, and some data were missing.
  • Patient numbers were small, both in the hospital series and in the TCGA data, which limited subgroup analysis. The authors said the TCGA findings should be considered with caution.
  • A large share of tumours could not be classified by the recommended cytological categories.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Epithelioid, Mesothelioma, Prognosis, Overall Survival, Hazard Ratio, Tubulopapillary, Multivariate Analysis.

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• A Histomorphologic Grading System That Predicts Overall Survival in Diffuse Malignant Peritoneal Mesothelioma With Epithelioid Subtype — K. Valente, A.U. Blackham, et al. (2016)
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• Histopathological features of epithelioid malignant pleural mesotheliomas in patients with extended survival — J. Paajanen, S. Laaksonen, et al. (2020)
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