Abstract

BackgroundTo develop cancer antigen-targeted immunotherapeutic strategies for malignant pleural mesothelioma (MPM), we investigated the individual and coexpressions of the cancer-associated antigens mesothelin (MSLN), cancer antigen 125 (CA125), and Wilms tumor 1 (WT1) in both epithelioid and non-epithelioid MPM.MethodsAll available hematoxylin and eosin-stained slides from patients who were diagnosed with MPM (1989-2010) were reviewed. We constructed tissue microarrays from 283 patients (epithelioid = 234; non-epithelioid = 49). Intensity and distribution for each antigen were assessed by immunohistochemistry.ResultsPositive expression of MSLN, CA125, and WT1 were demonstrated in 93%, 75%, and 97% of epithelioid MPM cases, and 57%, 33%, and 98% of non-epithelioid MPM cases, respectively. Triple- and double-positive antigen coexpressions were demonstrated in 72% and 23% of epithelioid MPM cases and 29% and 33% of non-epithelioid MPM cases, respectively. Complete absence of expression for all three antigens was demonstrated in <2% of MPM cases. More than two-thirds of MPM cases had ≥50% distribution of MSLN-positive cells and, among the remaining third, half had ≥50% distribution of WT1-positive cells. CA125/MSLN coexpression was observed in more than two-thirds of epithelioid MPM cases and one-third of non-epithelioid MPM cases.ConclusionA limited number of cancer-associated antigens can target almost all MPM tumors for immunotherapy.

Highlights

  • Malignant pleural mesothelioma (MPM) is an aggressive malignancy with a median survival of 9 to 12 months [1]

  • Positive expression of MSLN, cancer antigen 125 (CA125), and Wilms tumor 1 (WT1) were demonstrated in 93%, 75%, and 97% of epithelioid malignant pleural mesothelioma (MPM) cases, and 57%, 33%, and 98% of nonepithelioid MPM cases, respectively

  • Triple- and double-positive antigen coexpressions were demonstrated in 72% and 23% of epithelioid MPM cases and 29% and 33% of non-epithelioid MPM cases, respectively

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Summary

Introduction

Malignant pleural mesothelioma (MPM) is an aggressive malignancy with a median survival of 9 to 12 months [1]. Multimodality clinical trials for early-stage MPM have shown encouraging results [2,3,4,5,6], its benefits are limited [7, 8]. There is currently no clinically accepted targeted molecular therapy for MPM even though multiple clinical and preclinical studies have attempted to target recently discovered molecular alterations and gene overexpressions [11]. To develop cancer antigen-targeted immunotherapeutic strategies for malignant pleural mesothelioma (MPM), we investigated the individual and coexpressions of the cancer-associated antigens mesothelin (MSLN), cancer antigen 125 (CA125), and Wilms tumor 1 (WT1) in both epithelioid and non-epithelioid MPM

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