ORIGINAL ARTICLE Clinical impact of TP53 alterations in adrenocortical carcinomas Jens Waldmann & Nikolaos Patsalis & Volker Fendrich & Peter Langer & Wolfgang Saeger & Brunhilde Chaloupka & Annette Ramaswamy & Martin Fassnacht & Detlef K. Bartsch & Emily P. Slater Received: 19 July 2011 /Accepted: 24 October 2011 /Published online: 29 December 2011 # Springer-Verlag 2011 Abstract Background To evaluate the role of somatic TP53 muta- tions and to correlate somatic and germline mutations with results of immunostaining, a large cohort of ACC patients was analyzed. Patients and methods Patients with ACC who underwent potential curative surgery at the authors’ department were screened for TP53 somatic and germline mutations in exons 5, 6, 7, 8, and 10 by DHPLC analysis. Aberrant samples were further analyzed by direct sequencing. Immunostain- ing was performed on corresponding paraffin sections in all patients. Complete clinical and follow-up data were correlated with the status of TP53. Results Thirty ACC patients were included. Four of 30 patients showed aberrant DHPLC configuration and direct sequencing confirmed 2 (7%) germline mutations (R337H, R248W), 1 (3%) somatic mutation (R213X), and 1 (3%) noncoding polymorphism (g.17708 A>T). The only patient with a positive family history harbored a TP53 mutation. Tumors of the three patients with mutations showed aberrant p53 expression in more than 10% of cells by immunostaining, compared to only 3 of 27 patients without mutations (p =0.009). Aberrant p53 expression (>5%) was detected in 12/30 (40%) ACCs. The latter was associated with an increased Ki67 and van Slooten index (p ≤ 0.001; p = 0.020). Disease-free survival decreased significantly in patients with aberrant p53 IHC of more than 5% of cells (65.7±12.4 vs. 26.6±8.7 months; p =0.043 log rank test). Conclusions Patients with ACC revealed aberrant expres- sion of p53 in 40%, and mutations were identified in 25% of these patients. Therefore aberrant p53 expression should be considered an indicator for genetic testing. A subgroup of apparently sporadic ACC is caused by TP53 germline mutations, and family history is a strong indicator for p53 germline mutations. Keywords Adrenocortical cancer . Adrenal cancer . TP53 . Adrenalectomy Introduction Adrenocortical carcinomas (ACC) arise from the adrenal cortex and are responsible for 0.2% of cancer-related deaths [1]. The prognosis varies considerably with an overall 5- year survival rate ranging from 16% to 60% [2, 3]. This This work was presented at the ESES workshop in Lyon, France, May 2011. J. Waldmann (*) : N. Patsalis : V. Fendrich : P. Langer : B. Chaloupka : D. K. Bartsch : E. P. Slater Department of Visceral, Thoracic and Vascular Surgery, University Hospital Giessen and Marburg, Baldingerstraße, 35043 Marburg, Germany e-mail: jwaldman@med.uni-marburg.de N. Patsalis Department of Surgery, University of Cologne, Cologne, Germany W. Saeger Department of Pathology, Marienkrankenhaus, Hamburg, Germany A. Ramaswamy Department of Pathology, University Hospital Giessen and Marburg, Marburg, Germany M. Fassnacht Department of Internal Medicine, Division of Diabetology and Endocrinology, University Hospital Wuerzburg, Wuerzburg, Germany Langenbecks Arch Surg (2012) 397:209–216 DOI 10.1007/s00423-011-0868-6