TY - JOUR A1 - Lippert, Juliane A1 - Fassnacht, Martin A1 - Ronchi, Cristina L. T1 - The role of molecular profiling in adrenocortical carcinoma JF - Clinical Endocrinology N2 - Adrenocortical carcinoma (ACC) is a rare, aggressive cancer with still partially unknown pathogenesis, heterogenous clinical behaviour and no effective treatment for advanced stages. Therefore, there is an urgent clinical unmet need for better prognostication strategies, innovative therapies and significant improvement of the management of the individual patients. In this review, we summarize available studies on molecular prognostic markers and markers predictive of response to standard therapies as well as newly proposed drug targets in sporadic ACC. We include in vitro studies and available clinical trials, focusing on alterations at the DNA, RNA and epigenetic levels. We also discuss the potential of biomarkers to be implemented in a clinical routine workflow for improved ACC patient care. KW - adrenocortical cancer KW - biomarkers KW - precision medicine KW - prognosis KW - targeted treatment Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258382 VL - 97 IS - 4 ER - TY - JOUR A1 - Basile, Vittoria A1 - Puglisi, Soraya A1 - Altieri, Barbara A1 - Canu, Letizia A1 - Libè, Rossella A1 - Ceccato, Filippo A1 - Beuschlein, Felix A1 - Quinkler, Marcus A1 - Calabrese, Anna A1 - Perotti, Paola A1 - Berchialla, Paola A1 - Dischinger, Ulrich A1 - Megerle, Felix A1 - Baudin, Eric A1 - Bourdeau, Isabelle A1 - Lacroix, André A1 - Loli, Paola A1 - Berruti, Alfredo A1 - Kastelan, Darko A1 - Haak, Harm R. A1 - Fassnacht, Martin A1 - Terzolo, Massimo T1 - What is the optimal duration of adjuvant mitotane therapy in adrenocortical carcinoma? An unanswered question JF - Journal of Personalized Medicine N2 - A relevant issue on the treatment of adrenocortical carcinoma (ACC) concerns the optimal duration of adjuvant mitotane treatment. We tried to address this question, assessing whether a correlation exists between the duration of adjuvant mitotane treatment and recurrence-free survival (RFS) of patients with ACC. We conducted a multicenter retrospective analysis on 154 ACC patients treated for ≥12 months with adjuvant mitotane after radical surgery and who were free of disease at the mitotane stop. During a median follow-up of 38 months, 19 patients (12.3%) experienced recurrence. We calculated the RFS after mitotane (RFSAM), from the landmark time-point of mitotane discontinuation, to overcome immortal time bias. We found a wide variability in the duration of adjuvant mitotane treatment among different centers and also among patients cared for at the same center, reflecting heterogeneous practice. We did not find any survival advantage in patients treated for longer than 24 months. Moreover, the relationship between treatment duration and the frequency of ACC recurrence was not linear after stratifying our patients in tertiles of length of adjuvant treatment. In conclusion, the present findings do not support the concept that extending adjuvant mitotane treatment over two years is beneficial for ACC patients with low to moderate risk of recurrence. KW - mitotane KW - adjuvant treatment KW - adrenocortical cancer KW - recurrence KW - recurrence free survival KW - timing Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236507 SN - 2075-4426 VL - 11 IS - 4 ER - TY - JOUR A1 - Altieri, Barbara A1 - Sbiera, Silviu A1 - Della Casa, Silvia A1 - Weigand, Isabel A1 - Wild, Vanessa A1 - Steinhauer, Sonja A1 - Fadda, Guido A1 - Kocot, Arkadius A1 - Bekteshi, Michaela A1 - Mambretti, Egle M. A1 - Rosenwald, Andreas A1 - Pontecorvi, Alfredo A1 - Fassnacht, Martin A1 - Ronchi, Cristina L. T1 - Livin/BIRC7 expression as malignancy marker in adrenocortical tumors JF - Oncotarget N2 - 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. KW - cancer KW - livin KW - BIRC7 KW - adrenocortical cancer KW - adrenal tumor KW - caspase-3 Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171887 VL - 8 IS - 6 ER -