Tryptase Mast Cells in Malignant Pleural Mesothelioma as an Independent Favorable Prognostic Factor

Introduction: Malignant pleural mesothelioma is a highly aggressive neoplasm with an incidence that is increasing world-wide. Mast cells are part of the innate immune system and have been associated with different solid tumors, but there is controversy surrounding their pro- and antitumorigenic effects in cancers. There are two subsets of human mast cells, resulting from the expression of different enzymes: tryptase positive mast cells and chymase positive mast cells. The purpose of this study was to determine the presence and prognostic significance of tumor infiltrating mast cells in mesothelioma. Methods: Tryptase and chymase mast cell counts were determined by immunohistochemistry in 60 patients with mesothelioma. All pathologic samples were from patients who underwent treatment with intrapleural preoperative interleukin-2 (18 x 10(6) IU/d for 3 days). After one day of recovery, patients underwent surgery. Pleural samples were also immunostained for CD34 to evaluate microvessel count. Results: High tryptase mast cells counts were found in the majority (73.3%) of the cases Studied, and the results were significantly associated with both overall survival (p = 0.02) and time to progression (p = 0.01). This finding was confirmed using multivariate analysis: a higher tryptase mast cells count emerged as an independent favorable prognostic factor (p = 0.02). However, tryptase mast cells count did not show significant correlation with microvessel count. Conclusions: These results suggest that tumor infiltrating tryptase mast cells, after interleukin-2 preoperative induction therapy, predict improved clinical outcome in patients with malignant pleural mesothelioma, and highlight the critical role of the local inflammatory response in mesothelioma cancer progression. Key Words: Malignant pleural mesothelioma, Mast cells, Tryptase, Immunohistochemistry, Prognosis.