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

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.

Figure 1

B7-H1-positive malignant mesothelioma, sarcomatoid type: Neoplastic spindle cells are growing in a haphazard and tumefactive pattern (A, A insert). The neoplastic cells show diffuse and strong membranous and cytoplasmic expression of B7-H1 (B, B insert). B7-H1-positive malignant mesothelioma, epithelioid type: Neoplastic epithelioid cells are invading into adipose tissue (C, C insert). The neoplastic cells are strongly and diffusely positive for B7-H1 with a predominant cytoplasmic and focal membranous staining pattern (D, D insert). B7-H1-negative malignant mesothelioma, biphasic type: Neoplastic spindle cells are growing in a tumefactive pattern. Islands of neoplastic epithelioid cells are also present (E, E insert). The neoplastic cells are negative for B7-H1 (F, F insert). Magnification × 100 (A-F), × 400 (A-F-inserts).

Figure 2. Survival in mesothelioma by B7-H1 expression

The survival of 106 patients with malignant pleural mesothelioma is shown based on B7-H1 expression. Two patients were censored. Median survival was 5 months (2-9.5 months interquartile range) for patients with B7-H1 expression and 14.5 months (9.25-19 months interquartile range; p<0.0001) for those without B7-H1 expression.