Nicolè, LorenzoCappellesso, RoccoSanavia, TizianaGuzzardo, VincenzaFassina, Ambrogio2018-05-302018Nicolè, Lorenzo, Rocco Cappellesso, Tiziana Sanavia, Vincenza Guzzardo, and Ambrogio Fassina. 2018. “MiR-21 over-expression and Programmed Cell Death 4 down-regulation features malignant pleural mesothelioma.” Oncotarget 9 (25): 17300-17308. doi:10.18632/oncotarget.24644. http://dx.doi.org/10.18632/oncotarget.24644.http://nrs.harvard.edu/urn-3:HUL.InstRepos:37067981Background: Differential diagnosis between malignant pleural mesothelioma (MPM) and benign mesothelial conditions is still challenging and there is a lack of useful markers. Programmed cell death 4 (PDCD4) is a well-known tumor suppressor gene in several cancers, its post-transcriptional activity is directly controlled by miR-21, whose over-expression has been recently reported in MPM compared to normal mesothelium. Aim of this study was to test this suppressor gene as a possible new marker of malignant transformation in mesothelial cells, as well as a new prognostic marker. Methods: PDCD4 nuclear expression was assessed by immunohistochemistry (IHC) in 40 non-neoplastic pleural (NNP) and 40 MPM formalin-fixed and paraffin-embedded specimens. PDCD4 and miR-21 expressions were analyzed by qRT-PCR in all cases. In situ hybridization (ISH) of miR-21 was performed in 5 representative cases of both groups. The prognostic relevance of PDCD4 was assessed in a public available gene expression dataset. Results: IHC showed that PDCD4 nuclear expression was significantly lower in MPM than in NNP. PDCD4 was down-regulated, whereas miR-21 was over-expressed in MPM cases compared to NNP ones. ISH detected miR-21 only in MPM specimens. Down-expression of PDCD4 was found significantly associated with short overall survival in publicly available data. Conclusions: These findings highlighted a switch between PDCD4 and miR-21 expression in MPM. Further studies should assess the diagnostic reliability of these two markers for MPM in biopsy and effusion specimens.en-USPDCD4miR-21malignant pleural mesotheliomaimmunohistochemistryprognosisJournal Article2018-05-3010.18632/oncotarget.24644