title: Livin/BIRC7 expression as malignancy marker in adrenocortical tumors.
abstract: Livin/BIRC7 is a member of the inhibitors of apoptosis proteins family, which are involved in tumor development through the inhibition of caspases. Aim was to investigate the expression of livin and other members of its pathway in adrenocortical tumors and in the adrenocortical carcinoma (ACC) cell line NCI-H295R.The mRNA expression of livin, its isoforms α and β, XIAP, CASP3 and DIABLO was evaluated by qRT-PCR in 82 fresh-frozen adrenal tissues (34 ACC, 25 adenomas = ACA, 23 normal adrenal glands = NAG). Livin protein expression was assessed by immunohistochemistry in 270 paraffin-embedded tissues (192 ACC, 58 ACA, 20 NAG). Livin, CASP3 and cleaved caspase-3 were evaluated in NCI-H295R after induction of livin overexpression.Relative livin mRNA expression was significantly higher in ACC than in ACA and NAG (0.060 ± 0.116 vs 0.004 ± 0.014 and 0.002 ± 0.009, respectively, p < 0.01), being consistently higher in tumors than in adjacent NAG and isoform β more expressed than α. No significant differences in CASP3, XIAP and DIABLO levels were found among these groups. In immunohistochemistry, livin was localized in both cytoplasm and nuclei. The ratio between cytoplasmic and nuclear staining was significantly higher in ACC (1.51 ± 0.66) than in ACA (0.80 ± 0.35) and NAG (0.88 ± 0.27; p < 0.0001). No significant correlations were observed between livin expression and histopathological parameters or clinical outcome. In NCI-H295R cells, the livin overexpression slightly reduced the activation of CASP3, but did not correlate with cell viability.In conclusion, livin is specifically over-expressed in ACC, suggesting that it might be involved in adrenocortical tumorigenesis and represent a new molecular marker of malignancy.
authors.affiliation: Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital of Wuerzburg, Germany.|Division of Endocrinology and Metabolic Diseases, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Altieri
authors.affiliation: Comprehensive Cancer Center Mainfranken, University of Wuerzburg, Germany.
authors.forename: Silviu
authors.initials: S
authors.lastname: Sbiera
authors.affiliation: Division of Endocrinology and Metabolic Diseases, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Della Casa
authors.affiliation: Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital of Wuerzburg, Germany.
authors.forename: Isabel
authors.initials: I
authors.lastname: Weigand
authors.affiliation: Comprehensive Cancer Center Mainfranken, University of Wuerzburg, Germany.|Department of Pathology, University of Wuerzburg, Germany.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Wild
authors.affiliation: Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital of Wuerzburg, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Steinhauer
authors.affiliation: Division of Anatomic Pathology and Histology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Fadda
authors.affiliation: Department of Urology, University Hospital of Wuerzburg, Germany.
authors.forename: Arkadius
authors.initials: A
authors.lastname: Kocot
authors.affiliation: Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital of Wuerzburg, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Bekteshi
authors.affiliation: Department of Anesthesiology and Critical Care, University Hospital of Wuerzburg, Germany.
authors.forename: Egle M
authors.initials: EM
authors.lastname: Mambretti
authors.affiliation: Department of Pathology, University of Wuerzburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.affiliation: Division of Endocrinology and Metabolic Diseases, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Pontecorvi
authors.affiliation: Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital of Wuerzburg, Germany.|Comprehensive Cancer Center Mainfranken, University of Wuerzburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Fassnacht
authors.affiliation: Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital of Wuerzburg, Germany.
authors.forename: Cristina L
authors.initials: CL
authors.lastname: Ronchi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000306:Adrenal Cortex Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D018268:Adrenocortical Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014162:Transfection; D015854:Up-Regulation; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C419866:BIRC7 protein, human; D014408:Biomarkers, Tumor; C412403:DIABLO protein, human; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: BIRC7; adrenal tumor; adrenocortical carcinoma; caspase-3; livin