High mesothelin expression by immunohistochemistry predicts improved survival in pleural mesothelioma.

Autor: Chu GJ; Gene and Stem Cell Therapy Program Centenary Institute, University of Sydney, Sydney, NSW, Australia.; Department of Clinical Immunology and Allergy, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.; Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia., Linton A; Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.; Department of Medical Oncology, Concord Hospital, Concord, NSW, Australia.; Asbestos Diseases Research Institute, Concord, NSW, Australia., Kao S; Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.; Asbestos Diseases Research Institute, Concord, NSW, Australia.; Department of Medical Oncology, Chris O'Brien Lifehouse, Camperdown, NSW, Australia., Klebe S; Asbestos Diseases Research Institute, Concord, NSW, Australia.; Department of Anatomical Pathology, Flinders University and SA Pathology, Adelaide, SA, Australia., Adelstein S; Department of Clinical Immunology and Allergy, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.; Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia., Yeo D; Gene and Stem Cell Therapy Program Centenary Institute, University of Sydney, Sydney, NSW, Australia.; Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.; Cell and Molecular Therapies, Royal Prince Alfred Hospital, Camperdown, NSW, Australia., Rasko JEJ; Gene and Stem Cell Therapy Program Centenary Institute, University of Sydney, Sydney, NSW, Australia.; Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.; Cell and Molecular Therapies, Royal Prince Alfred Hospital, Camperdown, NSW, Australia., Cooper WA; Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.; Department of Tissue Pathology and Diagnostic Oncology, NSW Health Pathology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.; School of Medicine, Western Sydney University, Sydney, NSW, Australia.
Jazyk: angličtina
Zdroj: Histopathology [Histopathology] 2023 Aug; Vol. 83 (2), pp. 202-210. Date of Electronic Publication: 2023 Apr 11.
DOI: 10.1111/his.14916
Abstrakt: Aims: Mesothelin (MSLN) is a cancer-associated antigen that is overexpressed in malignancies such as mesothelioma, pancreatic and ovarian cancer. It is also a target for novel personalised therapies, including antibodies, antibody-drug conjugates and chimeric antigen receptor T cells. Immunohistochemistry may predict those who would best respond to anti-mesothelin therapies and guide decisions in therapeutic strategy. This study aimed to assess the intensity and distribution of MSLN immunostaining in mesothelioma, and to determine the prognostic value of MSLN expression by histochemical-score (H-score).
Methods and Results: The MN1 anti-MSLN antibody was used to stain a formalin-fixed paraffin-embedded tissue microarray of histologically confirmed mesothelioma from 75 consecutive patients who had undergone pleurectomy with or without decortication. MSLN positivity, the staining intensity, distribution of staining and H-score were evaluated. The correlation of H-score with prognosis was investigated. Sixty-six per cent of epithelioid tumours were MSLN-positive (with expression in > 5% tumour cells). Of MSLN-expressing epithelioid tumours, 70.4% had moderate (2+) or strong (3+) intensity MSLN immunostaining, although only 37% of samples had staining in ≥ 50% of tumour cells. In multivariate analysis, MSLN H-score as a continuous variable and an H-score ≥ 33 were independent predictors of improved survival (P = 0.04 and P < 0.001, respectively).
Conclusions: MSLN expression was more heterogenous in epithelioid mesothelioma than reported previously. Therefore, it would be appropriate to perform an immunohistochemical assessment of MSLN expression to stratify and assess patient suitability for mesothelin-targeted personalised therapies, such as chimeric antigen receptor T cells.
(© 2023 The Authors. Histopathology published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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