209P - SMO mutation is a strong negative prognostic factor in malignant pleural mesothelioma

Date 15 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session Poster lunch
Topics Mesothelioma
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Presenter Diego Signorelli
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors D. Signorelli1, C. Proto2, M. Ganzinelli2, G. Lo Russo2, L. Botta3, A. Trama3, G. Pasello4, M. Tiseo5, G. Pelosi6, M. Garassino1
  • 1Medical Oncology, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milano/IT
  • 2Medical Oncology, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milano/IT
  • 3Department Of Preventive And Predictive Medicine, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milano/IT
  • 4Medical Oncology, Istituto Oncologico Veneto IRCCS, Padova/IT
  • 5Oncologia Medica, Azienda Ospedaliera di Parma, 43126 - Parma/IT
  • 6Pathology Department, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milano/IT



Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer, with median overall survival (OS) rarely exceeding 18 months and limited therapeutic options. However, about 10–15% patients have better prognosis with a longer OS. The aim of this study is to identify a gene profile able to divide short (SS) versus long-term survivors (LS).


Clinical data and formalin-fixed paraffin-embedded tissue samples from 57 MPM patients were retrospectively collected and analyzed; 36 months was the cut-off of OS chosen to divide patients in SS (N = 33) and LS (N = 24). DNA was obtained by manual microdissection and a panel of 21 genes (CDKN2, NF2, GSTM1, NAT2, BAP1, TERT, P53, PTCH1, SMO, LATS2, KEAP1, PI3K, KRAS, NRAS, STK11, WT1, FBXW7, CTNNB1, KIT, KDR AND REV3) was tested by using the PGM Ion Torrent platform. The expression of SMO and GLI proteins, involved in Hedgehog pathway, was evaluated by immunohistochemistry (IHC) in 11 cases. The hazard risk of death was calculated with the Cox Model.


The main clinical prognostic factors (age, sex, histotype, stage and treatment) were equally distributed among the two groups. The most frequent mutated genes were BAP-1 (24.5%), NF-2 (17.5%), p53 (14%), SMO (8.8%), PTCH1 (8.8%), KEAP1 (7%) and TERT (5.3%), considering the whole population; 31.6% of the patients were wild-type for this panel. Median OS was 13 months for SS, 47 months for LS. No major differences in gene profile were observed between LS and SS; however, SMO was mutated only in SS (16%). SMO mutation was a strong negative prognostic factor (HR 8.01; CI95% 2.79–22.98 p 


SMO mutation seems to identify a subset of MPM patients with worse prognosis. As SMO can be a target for specific inhibitors, further preclinical and clinical studies are ongoing to investigate the role of SMO and its effectors in MPM. This study was granted by AIRC.

Clinical trial identification

Legal entity responsible for the study

Marina Garassino




All authors have declared no conflicts of interest.