New Immunohistochemical Markers for Pleural Mesothelioma Subtyping

Our plain-English summary of New Immunohistochemical Markers for Pleural Mesothelioma Subtyping, by I. Di Stefano, G. Alì, A.M. Poma, et al (Diagnostics, 2023).

The study

• Authors: I. Di Stefano, G. Alì, A.M. Poma, R. Bruno, A. Proietti, C. Niccoli, C.C. Zirafa, F. Melfi, M.G. Mastromarino, M. Lucchi, G. Fontanini
• Journal: Diagnostics
• Published: 2023;13(18)
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Pleural mesothelioma (PM) comprises three main subtypes: epithelioid, biphasic and sarcomatoid, which have different impacts on prognosis and treatment definition. However, PM subtyping can be complex given the inter- and intra-tumour morphological heterogeneity. We aim to use immunohistochemistry (IHC) to evaluate five markers (Mesothelin, Claudin-15, Complement Factor B, Plasminogen Activator Inhibitor 1 and p21-activated Kinase 4), whose encoding genes have been previously reported as deregulated among PM subtypes. Immunohistochemical expressions were determined in a case series of 73 PMs, and cut-offs for the epithelioid and non-epithelioid subtypes were selected. Further validation was performed on an independent cohort (30 PMs). For biphasic PM, the percentage of the epithelioid component was assessed, and IHC evaluation was also performed on the individual components separately. Mesothelin and Claudin-15 showed good sensitivity (79% and 84%) and specificity (84% and 73%) for the epithelioid subtype. CFB and PAK4 had inferior performance, with higher sensitivity (89% and 84%) but lower specificity (64% and 36%). In the biphasic group, all markers showed different expression when comparing epithelioid with sarcomatoid areas. Mesothelin, Claudin-15 and CFB can be useful in subtype discrimination. PAI1 and PAK4 can improve component distinction in biphasic PM.

In plain English

This Italian study tested whether five proteins, detected by staining tumour tissue, could help tell apart the three subtypes of pleural mesothelioma: epithelioid, biphasic and sarcomatoid. The authors used 103 archived samples diagnosed from 2011 to 2022: 73 to choose cut-off values and 30 to test them. Asbestos exposure was not examined. In the first group, Mesothelin and Claudin-15 best separated epithelioid from non-epithelioid tumours. In the test group, accuracy was 0.83 (confidence interval 0.70 to 0.93) for Mesothelin and 0.80 (0.63 to 0.93) for Claudin-15. CFB had accuracy 0.80 (0.67 to 0.93) but specificity 0.64 (0.36 to 0.91). PAK4 performed worse, with accuracy 0.67 (0.53 to 0.80) and specificity 0.36 (0.09 to 0.64). PAI1 results in the test group did not match the first group. Within biphasic tumours, PAI1 and PAK4 were higher in sarcomatoid areas, and the other three markers were higher in epithelioid areas. The authors concluded that Mesothelin, Claudin-15 and CFB are useful for telling subtypes apart. They noted that no follow-up data were available. They also noted that the best cut-offs differed between the two groups for most markers.

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 laboratory study of archived tumour samples. A training cohort was used to choose marker cut-offs and an independent validation cohort was used to test them.
• Who was studied: 103 pleural mesothelioma samples diagnosed from 2011 to 2022 at Pisa University Hospital, Italy. The training cohort had 73 samples (31 epithelioid, 25 biphasic, 17 sarcomatoid). The validation cohort had 30 samples (11 epithelioid, 11 biphasic, 8 sarcomatoid). Patients had a median age of 72; 83 were male and 20 were female.
• Exposure: No asbestos exposure was assessed. The study measured five tissue markers by immunohistochemistry: Mesothelin, Claudin-15, Complement Factor B (CFB), Plasminogen Activator Inhibitor 1 (PAI1) and p21-activated kinase 4 (PAK4).
• Main results:
  • In the training cohort, Mesothelin and Claudin-15 had the largest areas under the curve for telling epithelioid from non-epithelioid tumours: 0.97 and 0.85
  • In the validation cohort, Mesothelin accuracy was 0.83 (0.70 to 0.93)
  • In the validation cohort, Claudin-15 accuracy was 0.80 (0.63 to 0.93)
  • In the validation cohort, Mesothelin specificity was 0.91 (0.73 to 1)
  • In the validation cohort, CFB accuracy was 0.80 (0.67 to 0.93), with sensitivity 0.89 for identifying the epithelioid subtype
  • In the validation cohort, CFB specificity was 0.64 (0.36 to 0.91)
  • In the validation cohort, PAK4 accuracy was 0.67 (0.53 to 0.80)
  • In the validation cohort, PAK4 specificity was 0.36 (0.09 to 0.64)
  • In the validation cohort, PAI1 was more expressed in epithelioid than in biphasic tumours, which did not match the training cohort
  • Within biphasic tumours, Mesothelin, CFB and Claudin-15 were higher in epithelioid areas than in sarcomatoid areas
  • Within biphasic tumours, PAI1 and PAK4 were higher in the sarcomatoid component than in the epithelioid component (p less than 0.0001)
  • Among epithelioid tumours, higher Mesothelin levels were associated with low tumour grade (p = 0.02)
• The authors' conclusion: The authors concluded that Mesothelin, Claudin-15 and CFB are useful for discriminating subtypes and are preferentially expressed in the epithelioid subtype
• Limitations the authors state:
  • Except for Claudin-15, the best cut-offs differed greatly between the training and validation cohorts, so the cut-offs may need further optimization
  • No clinical information or follow-up data were available, which limited assessment of the markers' prognostic value

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Epithelioid, Biphasic Mesothelioma, Sarcomatoid, Prognosis, Immunohistochemistry, Mesothelin, Non-epithelioid.

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