Comprehensive immunohistochemical study of mesothelin (MSLN) using different monoclonal antibodies 5B2 and MN-1 in 1562 tumors with evaluation of its prognostic value in malignant pleural mesothelioma

Our plain-English summary of Comprehensive immunohistochemical study of mesothelin (MSLN) using different monoclonal antibodies 5B2 and MN-1 in 1562 tumors with evaluation of its prognostic value in malignant pleural mesothelioma, by S. Inaguma, Z. Wang, J. Lasota, et al (Oncotarget, 2017).

The study

• Authors: S. Inaguma, Z. Wang, J. Lasota, M. Onda, P. Czapiewski, R. Langfort, J. Rys, J. Szpor, P. Waloszczyk, K. Okoń, W. Biernat, H. Ikeda, D.S. Schrump, R. Hassan, I. Pastan, M. Miettinen
• Journal: Oncotarget
• Published: 2017;8(16):26744-26754
• Cited by: 58 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Mesothelin (MSLN) is a glycophosphatidylinositol (GPI)-linked cell surface protein highly expressed in several types of malignant tumors sometimes in association with increased tumor aggressiveness and poor clinical outcome. In the present study, 1562 tumors were immunohistochemically analyzed for mesothelin expression using two different types of mouse monoclonal antibodies (5B2 and MN-1) to determine the clinical usefulness of mesothelin immunohistochemistry as well as to pinpoint potential targets for future anti-mesothelin therapy. Also, characterization of selected mesothelin-positive tumors was performed by immunohistochemistry and oncogene sequencing. Among the tumors analyzed, the highest frequencies of mesothelin-positivity were detected in ovarian serous carcinoma (90% in 5B2 and 94% in MN-1). Both antibodies showed frequent positivity in pancreatic adenocarcinoma (71% using 5B2 and 87% using MN-1) and malignant pleural mesothelioma (75% using 5B2 and 78% using MN-1). In malignant mesothelioma, overall survival was significantly longer in the cohort of patients with diffuse membranous expression of mesothelin (P < 0.001). Both antibodies showed positive staining in thymic carcinoma (77% in 5B2 and 59% in MN-1), however, no expression was detected in thymoma. No correlation was detected between mesothelin expression and mismatch repair system deficient phenotype or gene mutation (BRAF and RAS) status in gastrointestinal adenocarcinomas. Mesothelin immunohistochemistry may assist the differential diagnosis of thymoma vs. thymic carcinoma as well as prognostication of mesothelioma patients. Our results demonstrate that patients with solid tumors expressing mesothelin could be targeted by anti-mesothelin therapies.

In plain English

This laboratory study examined tumor tissue; it did not study asbestos exposure. The authors stained 1562 tumors of many types with two antibodies (5B2 and MN-1) that detect mesothelin, a cell-surface protein. Ovarian serous carcinoma was most often positive (90% with 5B2, 94% with MN-1). Of 143 malignant mesotheliomas, 75% (5B2) and 78% (MN-1) were positive, epithelioid tumors more often than biphasic or sarcomatoid ones. Among 66 mesothelioma patients with survival data, those whose tumors showed mesothelin on the membrane of every tumor cell lived longer. Median survival was 36.0 versus 10.0 months with 5B2, and 33.0 versus 9.0 months with MN-1. In a statistical model this pattern was associated with a lower risk of death (hazard ratio 0.36, 95% CI 0.21 to 0.64). The authors lacked information on disease stage and patients' general condition, so they could not say whether this pattern predicts survival on its own. None of 33 thymomas was positive. The authors concluded that mesothelin staining could aid prognosis in malignant pleural mesothelioma and help distinguish thymoma from thymic carcinoma.

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: Laboratory (immunohistochemical) study of archived tumor tissue samples, with a survival analysis of a subset of mesothelioma patients; additional mismatch-repair staining and gene sequencing in gastrointestinal adenocarcinomas
• Who was studied: 1562 anonymized surgical tumor specimens of many types, including 143 malignant mesotheliomas (115 epithelioid, 17 biphasic, 10 sarcomatoid), 79 ovarian serous carcinomas, 132 pancreatic ductal carcinomas, 17 thymic carcinomas and 33 thymomas. Survival was analyzed in 66 mesothelioma patients (50 male, 16 female; median age 61). The article does not state where or when the specimens were collected.
• Exposure: No asbestos or other exposure was studied. The factor examined was mesothelin protein staining in tumor tissue, detected with antibodies 5B2 and MN-1. Three MPF antibodies (MPF25, MPF44, MPF49) were also compared in a preliminary set of 218 tumors.
• Main results:
  • Malignant mesothelioma (143 cases): positive with 5B2 in 75% and with MN-1 in 78%
  • Malignant mesothelioma: diffuse mesothelin expression in 31% (45/143) with 5B2 and 40% (57/143) with MN-1
  • Epithelioid mesothelioma was positive more often (81% with 5B2, 84% with MN-1) than sarcomatoid (20% with each) and biphasic (65% with each)
  • Mesothelioma patients whose tumors showed diffuse membranous expression with 5B2 had median survival of 36.0 months, versus 10.0 months for those with heterogeneous or no expression (P = 0.002)
  • With MN-1, median survival was 33.0 months with diffuse membranous expression versus 9.0 months with heterogeneous or no expression (P less than 0.001)
  • In multivariable Cox regression of the mesothelioma patients, diffuse membranous expression (MN-1) was a favorable prognostic factor: HR 0.36 (95% CI 0.21 to 0.64; P less than 0.001)
  • In mesothelioma patients, mesothelin expression as such (as opposed to the diffuse pattern) showed no impact on survival (data not shown)
  • Ovarian serous carcinoma had the highest positivity: 90% with 5B2 and 94% with MN-1
  • Pancreatic invasive ductal carcinoma: membrane positivity in 87% with MN-1 versus 71% with 5B2
  • Thymic carcinoma (17 cases) was positive in 77% with 5B2 and 59% with MN-1 (membrane and/or cytoplasm). No thymomas (33 cases) were positive with either antibody.
  • No significant correlation between mismatch-repair deficiency and mesothelin expression in gastric (P = 0.08) or colorectal (P = 0.51) adenocarcinomas, and none with BRAF/RAS mutation status in 75 colorectal tumors
• The authors' conclusion: The authors concluded that mesothelin immunohistochemistry could be useful for predicting outcome in malignant pleural mesothelioma patients and may help distinguish thymoma from thymic carcinoma. They also concluded that differences between the two antibodies in some tumor types should be considered when selecting patients for anti-mesothelin therapies.
• Limitations the authors state:
  • The authors lacked detailed clinical information such as disease stage and performance status, so they could not say whether diffuse mesothelin expression is by itself an independent favorable prognostic factor
  • The authors stated that the survival finding needs validation in larger studies with defined patient characteristics

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: Mesothelin, Monoclonal Antibody, Pleural Mesothelioma, Immunohistochemistry, Ovarian Serous Carcinoma, Adenocarcinoma, Mesothelioma, Overall Survival.

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