@article{AltieriSbieraDellaCasaetal.2017, author = {Altieri, Barbara and Sbiera, Silviu and Della Casa, Silvia and Weigand, Isabel and Wild, Vanessa and Steinhauer, Sonja and Fadda, Guido and Kocot, Arkadius and Bekteshi, Michaela and Mambretti, Egle M. and Rosenwald, Andreas and Pontecorvi, Alfredo and Fassnacht, Martin and Ronchi, Cristina L.}, title = {Livin/BIRC7 expression as malignancy marker in adrenocortical tumors}, series = {Oncotarget}, volume = {8}, journal = {Oncotarget}, number = {6}, doi = {10.18632/oncotarget.14067}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171887}, pages = {9323-9338}, year = {2017}, 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.}, language = {en} } @article{RonchiSbieraVolanteetal.2014, author = {Ronchi, Cristina L. and Sbiera, Silviu and Volante, Marco and Steinhauer, Sonja and Scott-Wild, Vanessa and Altieri, Barbara and Kroiss, Matthias and Bala, Margarita and Papotti, Mauro and Deutschbein, Timo and Terzolo, Massimo and Fassnacht, Martin and Allolio, Bruno}, title = {CYP2W1 Is Highly Expressed in Adrenal Glands and Is Positively Associated with the Response to Mitotane in Adrenocortical Carcinoma}, doi = {10.1371/journal.pone.0105855}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-113096}, year = {2014}, abstract = {Background Adrenocortical tumors comprise frequent adenomas (ACA) and rare carcinomas (ACC). Human cytochrome P450 2W1 (CYP2W1) is highly expressed in some cancers holding the potential to activate certain drugs into tumor cytotoxins. Objective To investigate the CYP2W1 expression in adrenal samples and its relationship with clinical outcome in ACC. Material and Methods CYP2W1 expression was investigated by qRT-PCR in 13 normal adrenal glands, 32 ACA, 25 ACC, and 9 different non-adrenal normal tissue samples and by immunohistochemistry in 352 specimens (23 normal adrenal glands, 33 ACA, 239 ACC, 67 non-adrenal normal or neoplastic samples). Results CYP2W1 mRNA expression was absent/low in normal non-adrenal tissues, but high in normal and neoplastic adrenal glands (all P<0.01 vs non-adrenal normal tissues). Accordingly, CYP2W1 immunoreactivity was absent/low (H-score 0-1) in 72\% of non-adrenal normal tissues, but high (H-score 2-3) in 44\% of non-adrenal cancers, in 65\% of normal adrenal glands, in 62\% of ACAs and in 50\% of ACCs (all P<0.001 vs non-adrenal normal tissues), being significantly increased in steroid-secreting compared to non-secreting tumors. In ACC patients treated with mitotane only, high CYP2W1 immunoreactivity adjusted for ENSAT stage was associated with longer overall survival and time to progression (P<0.05 and P<0.01, respectively), and with a better response to therapy both as palliative (response/stable disease in 42\% vs 6\%, P<0.01) or adjuvant option (absence of disease recurrence in 69\% vs 45\%, P<0.01). Conclusion CYP2W1 is highly expressed in both normal and neoplastic adrenal glands making it a promising tool for targeted therapy in ACC. Furthermore, CYP2W1 may represent a new predictive marker for the response to mitotane treatment.}, language = {en} }