Greta Alì1, Nicla Borrelli, Giannini Riccardo, Agnese Proietti, Serena Pelliccioni, Cristina Niccoli, Laura Boldrini, Marco Lucchi, Alfredo Mussi, Gabriella Fontanini. 1. *Unit of Pathological Anatomy, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy; †Department of Surgical, Medical, Molecular Pathology, and Critical Area, Division of Pathological Anatomy, University of Pisa, Pisa, Italy; ‡Unit of Thoracic Surgery, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy; and §Department of Surgical, Medical, Molecular Pathology and Critical Area, Division of Thoracic Surgery, University of Pisa, Pisa, Italy.
Abstract
INTRODUCTION: Malignant pleural mesothelioma (MPM) is a highly aggressive neoplasm associated with asbestos exposure. Currently, the molecular mechanisms that induce MPM development are still unknown. The purpose of this study was to identify new molecular biomarkers for mesothelial carcinogenesis. METHODS: We analyzed a panel of 84 genes involved in extracellular matrix remodeling and cell adhesion by polymerase chain reaction (PCR) array in 15 samples of epithelioid mesothelioma and 10 samples of reactive mesothelial hyperplasia (MH; 3 of 25 samples were inadequate for mRNA analysis). To validate the differentially expressed genes identified by PCR array, we analyzed 27 more samples by immunohistochemistry, in addition to the 25 samples already studied. RESULTS: Twenty-five genes were differentially expressed in MPM and MH by PCR array. Of these we studied matrix metalloproteinase 7 (MMP7), MMP14, CD44, and integrin, alpha3 expression by immunohistochemistry in 26 epithelioid MPM and 26 MH samples from the entire series of 52 cases. We observed higher MMP14 and integrin, alpha3 expression in MPM samples compared with MH samples (p = 0.000002 and p = 0.000002, respectively). Conversely, CD44 expression was low in most (57.7%) mesothelioma samples but only in 11.5% of the MH samples (p = 0.0013). As regards MMP7, we did not observe differential expression between MH and MPM samples. CONCLUSIONS: We have extensively studied genes involved in cell adhesion and extracellular matrix remodeling in MPM and MH samples, gaining new insight into the pathophysiology of mesothelioma. Moreover, our data suggest that these factors could be potential biomarkers for MPM.
INTRODUCTION:Malignant pleural mesothelioma (MPM) is a highly aggressive neoplasm associated with asbestos exposure. Currently, the molecular mechanisms that induce MPM development are still unknown. The purpose of this study was to identify new molecular biomarkers for mesothelial carcinogenesis. METHODS: We analyzed a panel of 84 genes involved in extracellular matrix remodeling and cell adhesion by polymerase chain reaction (PCR) array in 15 samples of epithelioid mesothelioma and 10 samples of reactive mesothelial hyperplasia (MH; 3 of 25 samples were inadequate for mRNA analysis). To validate the differentially expressed genes identified by PCR array, we analyzed 27 more samples by immunohistochemistry, in addition to the 25 samples already studied. RESULTS: Twenty-five genes were differentially expressed in MPM and MH by PCR array. Of these we studied matrix metalloproteinase 7 (MMP7), MMP14, CD44, and integrin, alpha3 expression by immunohistochemistry in 26 epithelioid MPM and 26 MH samples from the entire series of 52 cases. We observed higher MMP14 and integrin, alpha3 expression in MPM samples compared with MH samples (p = 0.000002 and p = 0.000002, respectively). Conversely, CD44 expression was low in most (57.7%) mesothelioma samples but only in 11.5% of the MH samples (p = 0.0013). As regards MMP7, we did not observe differential expression between MH and MPM samples. CONCLUSIONS: We have extensively studied genes involved in cell adhesion and extracellular matrix remodeling in MPM and MH samples, gaining new insight into the pathophysiology of mesothelioma. Moreover, our data suggest that these factors could be potential biomarkers for MPM.
Authors: Seán B Lyne; Romuald Girard; Janne Koskimäki; Hussein A Zeineddine; Dongdong Zhang; Ying Cao; Yan Li; Agnieszka Stadnik; Thomas Moore; Rhonda Lightle; Changbin Shi; Robert Shenkar; Julián Carrión-Penagos; Sean P Polster; Sharbel Romanos; Amy Akers; Miguel Lopez-Ramirez; Kevin J Whitehead; Mark L Kahn; Mark H Ginsberg; Douglas A Marchuk; Issam A Awad Journal: JCI Insight Date: 2019-06-20
Authors: Viktoria Laszlo; Zsuzsanna Valko; Judit Ozsvar; Ildiko Kovacs; Tamas Garay; Mir Alireza Hoda; Thomas Klikovits; Paul Stockhammer; Clemens Aigner; Marion Gröger; Walter Klepetko; Walter Berger; Michael Grusch; Jozsef Tovari; Irene C Waizenegger; Balazs Dome; Balazs Hegedus Journal: J Mol Med (Berl) Date: 2018-12-11 Impact factor: 4.599