Use of circulating and tumor-infiltrating myelomonocytic cells to predict survival in human malignant pleural mesothelioma (MPM).

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10578 Background: MPM is a devastating cancer with limited effective therapies. Mesothelioma tumor cells produce high levels of monocyte stimulating factors that can be found in the serum and effusions of patients with MPM. We hypothesized that an increased number of myeloid cells in MPM patients correlates with advanced disease and has a negative influence on clinical outcome. Methods: We analyzed preoperative WBC and absolute monocyte count in 896 patients with MPM that were treated surgically at a single institution from 1991 to 2009. Separately, an immunohistochemical analysis of the macrophage antigen CD68 was performed on MPM tissues from 60 patients who underwent cytoreductive surgery. Data were analyzed via t-tests, Spearman correlation coefficients, and survival analyses. Results: 80% of patients were male and 66% of cases were of the epithelial histologic subtype. Preoperatively, 21% of patients had a high WBC (> 10,000 cells/uL) and 8.5% had a high monocyte count (> 800 cells/uL). Patients with epithelial histology survived significantly longer than those with non-epithelial histology (16.7 v 8.9 mo; p < 0.0001). Patients with a normal WBC survived significantly longer than those with a high WBC (14.6 v 8.3 mo, p < 0.0001) and patients with a normal monocyte count survived significantly longer than those with a high monocyte count (18.6 v 9.6 mo, p < 0.0001). Patients with non-epithelial histology were more likely to have a higher WBC (p < 0.001) and a higher number of circulating monocytes (p = 0.0003) than those with epithelial histology. In MPM tissue sections, macrophages were a striking component of the inflammatory infiltrate representing 27 ± 9% (5%-50%) of all nucleated cells. The number of tumor-infiltrating macrophages inversely correlated with survival (p = 0.009). Present in both tumor nests and stroma, a high presence of macrophages in either compartment was associated with worse outcome (p = 0.02 tumor nest, p = 0.01 stroma). Conclusions: An increased number of circulating monocytes or tumor-infiltrating macrophages portends poor overall survival in MPM. This may overlie a systemic immune response to this malignancy and provides a potential target for intervention. No significant financial relationships to disclose.