title: Expression of inhibitor-of-apoptosis protein family members in malignant mesothelioma.
abstract: Inhibitor-of-apoptosis proteins (IAPs) mediate cancer cell survival and chemoresistance. We analyzed the expressions of X-linked IAP (XIAP), survivin, and livin in malignant mesothelioma. Ten effusions were analyzed for XIAP, survivin, and livin expression using immunoblotting. Based on the immunoblotting results, 112 mesotheliomas from 94 patients (pleural, n = 77; peritoneal, n = 35; solid, n = 68; effusions, n = 44) were immunostained for XIAP and survivin expression. Results were analyzed for associations with anatomic site (pleura versus peritoneum), specimen type (solid versus effusion), proliferation (Ki-67 score), and survival. Immunoblotting showed expression of XIAP in 9 of 10 effusions and that of survivin in 4 of 10 effusions, but no expression of livin. Immunohistochemistry showed cytoplasmic XIAP expression in 71 of the 112 (63%) tumors. XIAP expression was significantly higher in peritoneal mesotheliomas than in pleural mesotheliomas (P = .001) and in effusions than in solid lesions (P = .017). Cytoplasmic survivin was found in 75 of the 112 (67%) tumors and showed no site-related difference. Nuclear survivin was expressed in 37 of the 112 (33%) tumors, with a trend for positive association with the Ki-67 score (P = .051). Nuclear survivin (P = .003) and Ki-67 (P = .013) were downregulated in effusions as compared with solid tumors. Higher XIAP expression and Ki-67 score were associated with a trend for poor overall survival (P = .064 for both) in the univariate analysis. XIAP and survivin, but not livin, are frequently expressed in malignant mesotheliomas. Nuclear survivin expression is reduced in effusions as compared with solid lesions concomitantly with reduced proliferation. XIAP is upregulated in mesothelioma effusions and peritoneal mesotheliomas, suggesting a prosurvival role in malignant mesothelioma cells, particularly at these anatomic sites.
authors.affiliation: Pathology Clinic, Rikshospitalet-Radiumhospitalet Medical Center, Oslo N-0310, Norway.
authors.forename: Lilach
authors.initials: L
authors.lastname: Kleinberg
authors.affiliation: Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo N-0369, Norway.
authors.forename: Agnes Kathrine
authors.initials: AK
authors.lastname: Lie
authors.affiliation: Pathology Clinic, Rikshospitalet-Radiumhospitalet Medical Center, Oslo N-0310, Norway.
authors.forename: Vivi Ann
authors.initials: VA
authors.lastname: Flørenes
authors.affiliation: Pathology Clinic, Rikshospitalet-Radiumhospitalet Medical Center, Oslo N-0310, Norway; Faculty Division Radiumhospitalet, Medical Faculty, University of Oslo, Oslo N-0316, Norway.
authors.forename: Jahn M
authors.initials: JM
authors.lastname: Nesland
authors.affiliation: Pathology Clinic, Rikshospitalet-Radiumhospitalet Medical Center, Oslo N-0310, Norway. Electronic address: ben.davidson@radiumhospitalet.no.
authors.forename: Ben
authors.initials: B
authors.lastname: Davidson
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D020169:Caspases; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D008297:Male; D008654:Mesothelioma / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D010534:Peritoneal Neoplasms / Q000378:metabolism; D016066:Pleural Effusion, Malignant / Q000378:metabolism; D010997:Pleural Neoplasms / Q000378:metabolism; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C107489:BIRC5 protein, human; C419866:BIRC7 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D020169:Caspases