ECE2015 Eposter Presentations Endocrine tumours (69 abstracts)
Inhibitor of apoptosis protein livin/BIRC7 in adrenocortical tumours
Barbara Altieri 1, , Silviu Sbiera 1 , Silvia Della Casa 2 , Sonja Steinhauer 1 , Vanessa Wild 3 , Guido Fadda 4 , Michaela Bekteshi 1 , Andreas Rosenwald 3 , Alfredo Pontecorvi 2 , Martin Fassnacht 1 , Bruno Allolio 1 & Cristina L Ronchi 1
1Endocrine and Diabetes Unit, Department of Internal Medicine I, University Hospital of Wuerzburg, Wuerzburg, Germany; 2Division of Endocrinology and Metabolic Diseases, Institute of Medical Pathology, Catholic University, Rome, Italy; 3Department of Pathology, University of Wuerzburg, Wuerzburg, Germany; 4Division of Anatomic Pathology and Histology, Catholic University, Rome, Italy.
Introduction: Adrenocortical tumours comprise frequent adenomas (ACA) and rare highly malignant carcinoma (ACC). Livin/ML-IAP/BIRC7 is a member of the inhibitors of apoptosis proteins family, which are involved in tumorigenesis, mostly through the inhibition of caspase-3. Aim of the study was to evaluate the expression of livin/BIRC7 in normal and neoplastic adrenal glands.
Methods: The mRNA expression of BIRC7, its isoforms livin α and livin β, and caspase-3 was evaluated by qRT-PCR in 84 fresh-frozen tissues (34 ACC, 25 ACA, 25 normal adrenal glands=NAG), including 19 paired samples of tumour and surrounding NAG. Additionally, livin protein expression was assessed by western blot analysis (WB) in 14 paired samples (eight ACA, six ACC) and by immunohistochemistry in 127 paraffin-embedded tissue sections (67 ACC, 45 ACA, 15 NAG). The relationship with several histopathological and clinical data was also evaluated.
Results: BIRC7 mRNA expression was similar between ACAs (0.01±0.01) and NAG (0.01±0.02), but significantly higher in ACCs (0.06±0.12, P<0.005 vs both ACA and NAG), the isoform β was more expressed than α in all the subgroups. Comparable results were obtained with WB. The caspase-3 was higher in ACA (0.024±0.012) than in ACC (0.017±0.011, P=0.05) and NAG (0.018±0.011, P=0.03). Livin cytoplasmatic immunostaining was relatively homogeneous (79.5% of more than 50% positive cells). Livin protein expression was higher in ACC than ACA and NAG (mean±S.D. H-score: 1.72±0.7 vs 1.58±0.5 vs 1.33±0.6, respectively; P=0.09), being even higher in ACC samples coming from first surgery (n=53, 1.8±0.7) than in those coming from recurrence (n=8, 1.25±0.5) or distant metastasis (n=6, 1.5±0.5) (P=0.0001). No significant correlation was observed with the histopathological and clinical data, including overall survival.
Conclusion: Our study demonstrates that livin/BIRC7 is specifically over-expressed in ACCs, suggesting that it may be involved in adrenocortical tumorigenesis. BIRC7 could represent a novel marker for malignancy and a potential target for therapeutic approaches in ACC.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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