title: CD146 and insulin-like growth factor 2 mRNA-binding protein 3 predict prognosis of asbestos-induced rat mesothelioma.
abstract: Malignant mesothelioma (MM), which is associated with asbestos exposure, is one of the most deadly tumors in humans. Early MM is concealed in the serosal cavities and lacks specific clinical symptoms. For better treatment, early detection and prognostic markers are necessary. Recently, CD146 and insulin-like growth factor 2 mRNA-binding protein 3 (IMP3) were reported as possible positive markers of MM to distinguish from reactive mesothelia in humans. However, their application on MM of different species and its impact on survival remain to be elucidated. To disclose the utility of these molecules as early detection and prognostic markers of MM, we injected chrysotile or crocidolite intraperitoneally to rats, thus obtaining 26 peritoneal MM and establishing 11 cell lines. We immunostained CD146 and IMP3 using paraffin-embedded tissues and cell blocks and found CD146 and IMP3 expression in 58% (15/26) and 65% (17/26) of MM, respectively, but not in reactive mesothelia. There was no significant difference in both immunostainings for overexpression among the three histological subtypes of MM and the expression of CD146 and IMP3 was proportionally associated. Furthermore, the overexpression of CD146 and/or IMP3 was proportionally correlated with shortened survival. These results suggest that CD146 and IMP3 are useful diagnostic and prognostic markers of MM.
authors.affiliation: Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Aichi, Japan.
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Okazaki
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Nagai
authors.forename: Shan H
authors.initials: SH
authors.lastname: Chew
authors.forename: Jiang
authors.initials: J
authors.lastname: Li
authors.forename: Satomi
authors.initials: S
authors.lastname: Funahashi
authors.forename: Tohru
authors.initials: T
authors.lastname: Tsujimura
authors.forename: Shinya
authors.initials: S
authors.lastname: Toyokuni
mesh_terms: D000818:Animals; D001194:Asbestos / Q000633:toxicity*; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D051929:CD146 Antigen / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D005260:Female; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D008297:Male; D008654:Mesothelioma / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN
chemical_list: D014408:Biomarkers, Tumor; D051929:CD146 Antigen; C530106:Ccnd1 protein, rat; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018972:Insulin-Like Growth Factor Binding Protein 3; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D001194:Asbestos; D019938:Cyclin D1