B7-H1 expression in malignant pleural mesothelioma is associated with sarcomatoid histology and poor prognosis

Our plain-English summary of B7-H1 expression in malignant pleural mesothelioma is associated with sarcomatoid histology and poor prognosis, by A.S. Mansfield, A.C. Roden, T. Peikert, et al (Journal of Thoracic Oncology, 2014).

The study

• Authors: A.S. Mansfield, A.C. Roden, T. Peikert, Y.M. Sheinin, S.M. Harrington, C.J. Krco, H. Dong, E.D. Kwon
• Journal: Journal of Thoracic Oncology
• Published: 2014;9(7):1036-1040
• Cited by: 187 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: B7 homolog 1 (B7-H1; aka programmed cell death 1 ligand 1) is a negative costimulatory molecule that is associated with poor prognosis in many tumor types. Given the poor prognosis and the limited treatments available for mesothelioma, we decided to examine B7-H1 expression and its association with survival in patients with mesothelioma.

Methods: Expression of B7-H1 was determined in 106 patients using a mouse monoclonal antihuman B7-H1 (clone 5H1-A3) antibody with immunohistochemistry. Positive expression was defined as ≥5% positively stained cells. Clinicopathologic features and survival were compared between B7-H1-positive and B7-H1-negative groups.

Results: Malignant mesotheliomas of 42 patients (40%) expressed B7-H1. Patients with B7-H1-postive tumors were less likely to be offered or undergo therapeutic surgery (p = 0.03). All sarcomatoid mesotheliomas except one desmoplastic subtype expressed B7-H1. Survival was significantly decreased for patients whose tumors expressed B7-H1 (5 months median, 2-9.5 months interquartile range) compared with those whose tumors did not (14.5 months, 9.25-19 months; p < 0.0001). In a multivariate model, B7-H1 expression and sarcomatoid mesothelioma remained significantly associated with worse survival (risk ratio 1.71, 95% confidence interval 1.03-2.78 [p = 0.04] and risk ratio 2.18, 1.08-4.23 [p = 0.03], respectively).

Conclusions: B7-H1 is expressed in a substantial proportion of malignant pleural mesotheliomas and is associated with poor survival. Almost all malignant pleural mesotheliomas with sarcomatoid differentiation expressed B7-H1. The expression of B7-H1 may have important therapeutic implications for the management of malignant pleural mesothelioma.

In plain English

This brief report from Mayo Clinic in Rochester, Minnesota, looked back at 106 patients diagnosed with malignant pleural mesothelioma between 1987 and 2003. The authors stained stored tumor tissue for B7-H1 (also called programmed cell death 1 ligand 1), a molecule that can hold back immune cells called T lymphocytes. Tumors with at least 5% stained cells counted as positive. Tumors of 42 patients (40%) were positive. All sarcomatoid mesotheliomas except one desmoplastic subtype were positive. Patients with positive tumors were less likely to have therapeutic surgery: 7 of 42 (17%) compared with 23 of 64 (36%). Median survival was 5 months for patients with positive tumors and 14.5 months for those with negative tumors. After adjusting for age, tumor type and surgery, B7-H1 expression (risk ratio 1.71, 95% confidence interval 1.03 to 2.78) and sarcomatoid type (risk ratio 2.18, 1.08 to 4.23) remained associated with worse survival. The authors concluded that B7-H1 is associated with poor survival and that drugs targeting it warrant exploration. They noted that their tissue methods may have underestimated B7-H1 expression. The article did not report asbestos exposure.

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 archived tumor tissue (immunohistochemistry) with retrospective chart review for clinical and survival data; published as a brief report
• Who was studied: 106 patients treated at Mayo Clinic in Rochester, Minnesota, and diagnosed with malignant pleural mesothelioma between January 1, 1987 and December 31, 2003, who had adequate tissue samples; 104 had died by last follow-up
• Exposure: The factor studied was expression of B7-H1 in tumor tissue, with positive defined as at least 5% stained cells. Asbestos or other environmental exposure was not reported.
• Main results:
  • Tumors of 42 of the 106 patients (40%) expressed B7-H1
  • All sarcomatoid mesotheliomas except one of the desmoplastic subtype expressed B7-H1 (16 sarcomatoid tumors in the B7-H1-positive group, 1 in the B7-H1-negative group). Epithelioid tumors made up 14 (33%) of the positive group and 54 (84%) of the negative group.
  • Patients with B7-H1-positive tumors were less likely to undergo therapeutic surgery: 7 (17%) compared with 23 (36%) of B7-H1-negative patients, p = 0.03, primarily because of extent of disease
  • Median survival was 5 months (interquartile range 2 to 9.5 months) for patients with B7-H1-positive tumors and 14.5 months (9.25 to 19 months) for those with B7-H1-negative tumors, p less than 0.0001
  • Among patients with epithelioid tumors, survival was 14 months with B7-H1-negative tumors and 6 months with B7-H1-positive tumors, but this difference was not statistically significant (p = 0.10)
  • After adjusting for age, histology and therapeutic surgery, B7-H1 expression remained associated with worse survival (risk ratio 1.71, 95% confidence interval 1.03 to 2.78, p = 0.04)
  • Sarcomatoid histology also remained associated with worse survival in the multivariate model (risk ratio 2.18, 1.08 to 4.23, p = 0.03)
• The authors' conclusion: The authors concluded that B7-H1 is expressed in a substantial proportion of malignant pleural mesotheliomas and is associated with poor survival, that almost all sarcomatoid tumors expressed it, and that agents targeting B7-H1 or its receptor PD-1 warrant exploration, especially for sarcomatoid mesothelioma
• Limitations the authors state:
  • The study used formalin-fixed paraffin-embedded tissue rather than fresh-frozen tissue, so the authors may have underestimated how often B7-H1 is expressed; they said the results should be validated prospectively with fresh-frozen tissue
  • Strict inclusion criteria limited the sample size

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Sarcomatoid, Histology, Prognosis, Mesothelioma, Monoclonal, Immunohistochemistry, Malignant Mesothelioma.

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