Survivin in Adrenocortical Tumors – Pathophysiological Implications and Therapeutic Potential

S. Sbiera; M. Kroiss; T. Thamm; M. Beyer; F. Majidi; D. Kuehner; M. Wobser; J. C. Becker; P. Adam; C. Ronchi; B. Allolio; M. Fassnacht

doi:10.1055/s-0032-1327750

Hormone and Metabolic Research, Inhaltsverzeichnis

Horm Metab Res 2013; 45(02): 137-146
DOI: 10.1055/s-0032-1327750

Humans, Clinical

Survivin in Adrenocortical Tumors – Pathophysiological Implications and Therapeutic Potential

S. Sbiera

¹Department of Internal Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, University of Würzburg, Würzburg, Germany

,

M. Kroiss

¹Department of Internal Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, University of Würzburg, Würzburg, Germany

,

T. Thamm

¹Department of Internal Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, University of Würzburg, Würzburg, Germany

,

M. Beyer

¹Department of Internal Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, University of Würzburg, Würzburg, Germany

,

F. Majidi

¹Department of Internal Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, University of Würzburg, Würzburg, Germany

,

D. Kuehner

¹Department of Internal Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, University of Würzburg, Würzburg, Germany

,

M. Wobser

²Department of Dermatology, University Hospital Würzburg, University of Würzburg, Würzburg, Germany

,

J. C. Becker

³Department of General Dermatology, Medical University of Graz, Graz, Austria

,

P. Adam

⁴Department of Pathology, University Hospital Tübingen, Tübingen, Germany

,

C. Ronchi

¹Department of Internal Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, University of Würzburg, Würzburg, Germany

,

B. Allolio

¹Department of Internal Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, University of Würzburg, Würzburg, Germany

,

M. Fassnacht

¹Department of Internal Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, University of Würzburg, Würzburg, Germany

⁵Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany

› Institutsangaben

Abstract

Treatment options for adrenocortical carcinoma (ACC) are very limited. In other solid tumors, small vaccination trials targeting the anti-apoptotic molecule survivin suggested immunological and clinical benefit in selected patients. Therefore, we investigated whether survivin might be a suitable target for immunotherapy in ACC. Survivin mRNA and protein expression was assessed in adrenal tissue specimens [by real-time-PCR in 29 ACC, 24 adrenocortical adenomas (ACA) and 12 normal adrenal glands; by immunohistochemistry in 167 ACCs, 15 ACA, and 5 normal adrenal glands]. Expression was correlated with clinical outcome using Kaplan–Meier and Cox regression analyses. The anti-apoptotic role of survivin was investigated in the SW13 ACC cell line using survivin siRNA. The presence of spontaneous survivin specific T-cells in peripheral blood was assessed by FACS dextramere staining in 29 ACC patients in comparison to healthy controls. Survivin mRNA in ACC was significantly overexpressed when compared with ACA or normal adrenal glands. Immunohistochemistry confirmed survivin protein expression in 97% of the ACCs. In 83% of samples, staining was moderate or high and clinical outcome in this subgroup showed a trend towards poorer prognosis [hazard ratio for death 2.28 (95% CI 0.99–5.28); p=0.053]. Survivin knockdown in SW-13 cell significantly increased the rate of apoptosis. Finally, spontaneous survivin-reactive T cells were detectable in 3 of 29 ACC patients. In conclusion, our data suggest that survivin could play an important role in the anti-apoptotic mechanisms in ACC and provide first hints that targeting survivin might be an interesting new therapeutic approach in this rare disease.

Key words

adrenocortical carcinoma - BIRC5 - apoptosis - prognosis - therapy

Volltext

Referenzen

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