Chronic inflammation in tumor stroma is an independent predictor of prolonged survival in epithelioid malignant pleural mesothelioma patients

Abstract

This study aims to determine whether a semi-quantitative assessment of inflammatory response in tumor and stroma on routine hematoxylin and eosin-stained (H&E) slides can predict survival in patients with epithelioid malignant pleural mesothelioma (MPM). H&E sections of 175 epithelioid MPM specimens from a single institution (1989–2009) were reviewed. Patients who received neoadjuvant chemotherapy were excluded from analysis. Each tumor was histologically assessed for acute and chronic inflammatory response both within the tumor and the stromal component. Inflammatory response was graded: low (none to mild infiltrate) or high (moderate to severe infiltrate). Log-rank test and Cox proportional hazards regression were used to investigate the association between the degree of inflammation (acute/tumor, acute/stroma, chronic/tumor, and chronic/stroma) and overall survival (OS). Patients with high chronic inflammatory response in stroma (n = 59) had improved survival compared to low (n = 116) (median OS = 19.4 vs. 15.0 months, P = 0.01). This prognostic stratification remained significant in stage III patients (median OS = 16.0 vs. 9.3 months, P = 0.03). In multivariate analysis, chronic inflammation in stroma was an independent predictor of survival (HR = 0.659, 95% CI 0.464–0.937, P = 0.02). While high degree of chronic inflammatory cell infiltration in the stromal component was associated with improved overall survival, degree of other inflammatory responses did not show significant correlation with OS. Our study for the first time investigates inflammatory response in tumor and stroma and not only suggests the prognostic value of inflammatory response in epithelioid MPM but also provides rationale for investigation of immunotherapy to benefit epithelioid MPM patients.

The value of inflammatory parameters in the prognosis of malignant mesothelioma

“…20 In contrast, in 44 patients with MM treated with surgical procedures, NLR !5 was not found to be associated with MM prognosis. 21 Other potentially prognostic inflammatory markers are red cell distribution width (RDW) and mean platelet volume (MPV). RDW is a measure of the variability in the size of circulating erythrocytes, 22 and is routinely reported with complete blood count.…”

The tumor immune microenvironment in octogenarians with stage I non-small cell lung cancer

“…We [20][21][22][23] and others [15][16][17]19 have shown the prognostic significance of the tumor immune microenvironment in solid malignancies. To the best of our knowledge, there have been no published studies on the association between tumor-infiltrating immune cells and elderly patients in either NSCLC or other solid malignancies.…”

The Role of Inflammation in Development and Therapy of Malignant Mesothelioma

“…A study on 175 epithelioid MPM specimens investigated inflammatory responses in tumors and stroma and suggested a positive prognostic value of inflammatory response in the stroma of epithelioid MPM. Interestingly, inflammation within the tumor, as opposed to the stroma, was associated with a vascular invasion, a poor prognostic feature (Suzuki et al, 2011). Collectively, these studies provide rationale for investigating immunotherapy to benefit epithelioid MPM patients.…”