Lung Cancer (2005) 48, 211—216 Quantitative evaluation of the apoptosis regulating genes Survivin, Bcl-2 and Bax in inflammatory and malignant pleural lesions Monica Falleni a,*,1 , Caterina Pellegrini a,1 , Antonio Marchetti b , Massimo Roncalli c , Mario Nosotti d , Alessandro Palleschi d , Luigi Santambrogio d , Guido Coggi a,e , Silvano Bosari a a Department of Medicine Surgery and Dentistry, Division of Pathology, University of Milan, AO San Paolo e IRCCS Ospedale Maggiore, Via A. Di Rudin` ı 8, 20142 Milan, Italy b Department of Oncology and Neurosciences, University of Chieti, Italy c Division of Pathology, University of Milan, Humanitas Clinical Institute, Rozzano, Milan, Italy d Unit of Thoracic Surgery, IRCCS Ospedale Maggiore, Milan, Italy e Interuniversity Center of Cancer Research, Milan, Italy Received 5 August 2004; received in revised form 14 October 2004; accepted 14 October 2004 KEYWORDS Gene expression; Survivin; Bcl-2; Bax; Bcl-2/Bax ratio; Malignant mesothelioma; Real-timeRT-PCR Summary Aim: Weaimedtoidentifydefectsintheprogrammedcelldeathpathwaythatcanbe relatedtopleuralmalignantmesothelioma(MM)unresponsivenesstochemotherapy. Materials and methods: WequantifiedmRNAlevelsoftheapoptosisregulatinggenes Survivin, member of the IAP family, Bcl-2 and Bax, members of the Bcl-2 family. We studied 22 non-neoplastic pleural samples, comprising normal and inflammatory tissue specimens, and 42 pleural MMs using real-time RT-PCR. Results: Very low mRNA levels of each apoptotic gene were detected in all nor- mal pleural samples. All three genes displayed increased mRNA levels in inflamma- tory and tumor specimens. Survivin levels in pleuritis and MMs were significantly in- creased (333% and 908%, respectively) compared to normal counterparts (p =0.0147 and 0.00349, respectively). Bcl-2 and Bax levels were increased in inflammatory pleural samples (394%, p =0.001 and 188%, p =ns, respectively) and in MMs (94%, p =nsand88%, p =0.0163, respectively). The Bcl-2/Bax ratio was higher in pleuritis thaninMMs,comparedtonormalpleurae(441%, p =nsand22%, p =ns,respectively); the difference between Bcl-2/Bax ratio in inflammatory and neoplastic pleural sam- ples was significant (p =0.00375). Conclusions: These results suggest that apoptotic defects in pleural MMs are linked to increased levels of Survivin, whereas variations in Bcl-2 and Bax expression Abbreviation: MM, malignant mesothelioma * Corresponding author. Tel.: +39 02 81844600; fax: +39 02 50323168. E-mail address: monica.falleni@unimi.it (M. Falleni). 1 They contributed equally to this work. 0169-5002/$ — see front matter © 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.lungcan.2004.10.003