Background: The aim of this study was to determine both prognostic clinical-morphological and predictive biomolecular factors affecting course of disease and survival in malignant pleural mesothelioma (MPM). Methods: We retrospectively analyzed (2004-2014) clinical and pathological data of 108 consecutive patients with diagnosis of MPM. Age, stage (WHO 2015), chemotherapy, histotype, nuclear atypia, mitotic count (1/mm2), Ki-67 percentage and 9p21 (p16/CDKN2A) deletion (43 cases) were analyzed and correlated to survival. Survival was evaluated with Kaplan-Meier method and statistical significance with Log-Rank test (SPSS software, 18.0). Results: There were 83 (76.9%) males, 25 (23.1%) females (ratio 3.3/1); median age at diagnosis was 68 (mean 67.2±9.8; range 42-90) years; 94 (87%) patients had asbestos exposure. Overall median survival was 13.3 (mean 19.15±22.4; range 1-136) months. Mean survival (months) was: 30.2±4.6 and 12.4±1.6 in age ≤ 65 and > 65 years (p=0.0001); 24±4.3 in stage I, 21.3±4.5 in II, 21.1±5.8 in III, 9.7±1.7 in IV (p=0.005); 25.9±2.8 and 5±1.3 in patients receiving complete (n=73) and palliative (n=35) chemotherapy (p=0.0001); 21.4±2.5, 11.6±2.7 and 8.5±2.3 in epithelioid, biphasic and sarcomatoid histotypes (p=0.0001); 26.3±3.3 and 12.4±2.5 in moderate and severe nuclear atypia (p=0.0001); 26±3.4 and 9.9±1,3 in low (≤ 5 mm2) and high (> 5 mm2) mitotic count (p=0.0001); 27.2±3.4 and 9.1±1.1 in low (≤ 25%) and high (> 25%) Ki-67 expression (p=0.0001); 35.8±7.7 in absence of p16/CDKN2A deletion, 17.4±3.4 in heterozygous and 8.9±1.9 in homozygous deletion (p=0.0001). Mean survival (months) in patients receiving complete chemotherapy compared to those receiving palliative one was: stage I 30.7±5.4 and 8.2±4.4 (p=0.0001), stage II 25.8±5.3 and 4.2±1.0 (p=0.0001), stage III 25.2±6.8 and 3.0±0.4 (p=0.0001), stage IV 17.7±2.5 and 3.8±0.7 (p=0.0001). Conclusion: Age, stage, chemotherapy, histotype, nuclear atypias, mitoses, proliferating index and loss of 9p21 gene are predictors of survival in MPM and strongly influence the therapeutic strategy. Chemotherapy significantly affects survival in different stages of MPM
