An integrative histopathologic clustering model based on immuno-matrix elements to predict the risk of death in malignant mesothelioma

Our plain-English summary of An integrative histopathologic clustering model based on immuno-matrix elements to predict the risk of death in malignant mesothelioma, by M.L. Balancin, W.R. Teodoro, C. Farhat, et al (Cancer Medicine, 2020).

The study

• Authors: M.L. Balancin, W.R. Teodoro, C. Farhat, T.J. de Miranda, A.K. Assato, N.A. de Souza Silva, A.P. Velosa, R. Falzoni, A.M. Ab'Saber, A.C. Roden, V.L. Capelozzi
• Journal: Cancer Medicine
• Published: 2020;9(13):4836-4849
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Objective: Previous studies have reported a close relationship between malignant mesothelioma (MM) and the immune matricial microenvironment (IMM). One of the major problems in these studies is the lack of adequate adjustment for potential confounders. Therefore, the aim of this study was to identify and quantify risk factors such as IMM and various tumor characteristics and their association with the subtype of MM and survival.

Methods: We examined IMM and other tumor markers in tumor tissues from 82 patients with MM. These markers were evaluated by histochemistry, immunohistochemistry, immunofluorescence, and morphometry. Logistic regression analysis, cluster analysis, and Cox regression analysis were performed.

Results: Hierarchical cluster analysis revealed two clusters of MM that were independent of clinicopathologic features. The high-risk cluster included MM with high tumor cellularity, high type V collagen (Col V) fiber density, and low CD8+ T lymphocyte density in the IMM. Our results showed that the risk of death was increased for patients with MM with high tumor cellularity (OR = 1.63, 95% CI = 1.29-2.89, P = .02), overexpression of Col V (OR = 2.60, 95% CI = 0.98-6.84, P = .04), and decreased CD8 T lymphocytes (OR = 1.001, 95% CI = 0.995-1.007, P = .008). The hazard ratio for the high-risk cluster was 2.19 (95% CI = 0.54-3.03, P < .01) for mortality from MM at 40 months.

Conclusion: Morphometric analysis of Col V, CD8+ T lymphocytes, and tumor cellularity can be used to identify patients with high risk of death from MM.

© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

In plain English

This retrospective Brazilian study examined tumor tissue from 82 patients with malignant mesothelioma (73 epithelioid, 9 sarcomatoid) from hospital records, 2008 to 2019. All had stage III or IV disease; 49 died of recurrence or metastases. Using staining and computer image analysis, the authors grouped patients by tissue features. A cluster analysis separated 15 high-risk patients, with denser tumor cells, more type V collagen and fewer CD8+ T lymphocytes, from 67 low-risk patients. The high-risk group's median survival was 12 months; the low-risk group's was not reached. The abstract reports a hazard ratio of 2.19 (95% CI 0.54 to 3.03) for death at 40 months, high-risk versus low-risk; a table calls this an odds ratio, and another gives an adjusted hazard ratio of 1.28 (95% CI 0.60 to 2.75). Asbestos exposure was linked to death within 40 months before adjustment (HR 1.88, 95% CI 1.004 to 3.52) but not after (HR 1.02, 95% CI 0.51 to 2.05). The authors noted few sarcomatoid cases and short follow-up. They concluded that type V collagen and CD8+ T lymphocytes in highly cellular tumors might be therapy targets.

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: Retrospective study of tumor tissue (tissue microarray, staining, computer image analysis) with cluster and survival analyses
• Who was studied: 82 patients with malignant mesothelioma (73 epithelioid, 9 sarcomatoid; 62 pleural, 20 extrapleural), all stage III or IV, from hospital records 2008 to 2019, São Paulo, Brazil
• Exposure: Not an asbestos exposure study. It measured markers in the tumor and the surrounding tissue: tumor cellularity, collagen types I and V, immune cells (CD4, CD8, CD20, CD68) and other proteins. Asbestos exposure was recorded only as yes or no, and no fiber type is given.
• Main results:
  • 49 patients died of recurrence or metastases (printed as 56%).
  • Cluster analysis identified 67 patients in cluster I (low risk) and 15 in cluster II (high risk).
  • The high-risk cluster was defined by tumor cellularity above 80.6 cells/mm2, type V collagen density above 7.75 fibers/mm3 and CD8 T lymphocytes below 99.77 cells/mm2.
  • The abstract gives a hazard ratio of 2.19 (95% CI 0.54-3.03, P less than .01) for death from mesothelioma at 40 months in the high-risk cluster. Table 4 lists the same figure in a column headed OR (odds ratio). The authors describe it as twice the risk of cluster I.
  • Table 5 (risk of death at 40 months) gives a hazard ratio for high-risk vs low-risk cluster of 1.32 (95% CI 0.68-2.58, P .01) in univariate analysis and 1.28 (95% CI 0.60-2.75, P .01) in multivariate analysis.
  • Median survival was 12 months for the high-risk cluster (P = .03). For the low-risk cluster, median survival was not reached and mean survival was 21 months.
  • For risk of death at 40 months, asbestos exposure (yes vs no) had a hazard ratio of 1.88 (95% CI 1.004-3.52, P .04) in univariate analysis and 1.02 (95% CI 0.51-2.05, P .95) in multivariate analysis.
  • Epithelioid tumors had more CD8+ T lymphocytes than sarcomatoid tumors (mean 62.40 vs 6.54 cells/mm2, P less than .005).
• The authors' conclusion: The authors concluded that in their cohort, asbestos-related mesotheliomas had a low mutational burden and a distinct tumor microenvironment rather than genetic abnormalities. They also concluded that type V collagen density and CD8+ T lymphocytes in tumors with high cellularity might be potential targets for therapies.
• Limitations the authors state:
  • Small number of sarcomatoid cases (9), collected retrospectively, with a maximum follow-up of 40 months
  • The tissue microarray format may have under- or overrepresented variables because of variation within tumors
  • No data on responses to immune checkpoint inhibitor therapies

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Tumor Marker, Immunohistochemistry, Collagen, Hazard Ratio.

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