@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}
}
@article{SbieraRonchiLeichetal.2013,
  author    = {Sbiera, Silviu and Ronchi, Cristina L. and Leich, Ellen and Henzel, Katharina and Rosenwald, Andreas and Allolio, Bruno and Fassnacht, Martin},
  title     = {Single Nucleotide Polymorphism Array Profiling of Adrenocortical Tumors - Evidence for an Adenoma Carcinoma Sequence?},
  series = {PLoS ONE},
  journal   = {PLoS ONE},
  doi       = {10.1371/journal.pone.0073959},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97218},
  year      = {2013},
  abstract  = {Adrenocortical tumors consist of benign adenomas and highly malignant carcinomas with a still incompletely understood pathogenesis. A total of 46 adrenocortical tumors (24 adenomas and 22 carcinomas) were investigated aiming to identify novel genes involved in adrenocortical tumorigenesis. High-resolution single nucleotide polymorphism arrays (Affymetrix) were used to detect copy number alterations (CNAs) and copy neutral losses of heterozygosity (cnLOH). Genomic clustering showed good separation between adenomas and carcinomas, with best partition including only chromosome 5, which was highly amplified in 17/22 malignant tumors. The malignant tumors had more relevant genomic aberrations than benign tumors, such as a higher median number of recurrent CNA (2631 vs 94), CNAs >100 Kb (62.5 vs 7) and CN losses (72.5 vs 5.5), and a higher percentage of samples with cnLOH (91\% vs 29\%). Within the carcinoma cohort, a precise genetic pattern (i.e. large gains at chr 5, 7, 12, and 19, and losses at chr 1, 2, 13, 17, and 22) was associated with a better prognosis (overall survival: 72.2 vs 35.4 months, P=0.063). Interestingly, >70\% of gains frequent in beningn were also present in malignant tumors. Notch signaling was the most frequently involved pathway in both tumor entities. Finally, a CN gain at imprinted "IGF2" locus chr 11p15.5 appeared to be an early alteration in a multi-step tumor progression, followed by the loss of one or two alleles, associated with increased IGF2 expression, only in carcinomas. Our study serves as database for the identification of genes and pathways, such as Notch signaling, which could be involved in the pathogenesis of adrenocortical tumors. Using these data, we postulate an adenoma-carcinoma sequence for these tumors.},
  language  = {en}
}
@article{JohanssenHahnerSaegeretal.2010,
  author    = {Johanssen, Sarah and Hahner, Stefanie and Saeger, Wolfgang and Quinkler, Marcus and Beuschlein, Felix and Dralle, Henning and Haaf, Michaela and Kroiss, Matthias and Jurowich, Christian and Langer, Peter and Oelkers, Wolfgang and Spahn, Martin and Willenberg, Holger S. and Maeder, Uwe and Allolio, Bruno and Fassnacht, Martin},
  title     = {Deficits in the Management of Patients With Adrenocortical Carcinoma in Germany},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-85897},
  year      = {2010},
  abstract  = {Background: Adrenocortical carcinoma (ACC) is a rare tumor with a poor prognosis. Often, the physicians who first treat patients with ACC have no prior experience with the disease. The aim of our study was to evaluate the quality of medical care for patients with ACC in Germany. Methods: Data from the German ACC registry were analyzed with regard to the patients' preoperative diagnostic evaluation, histopathological reporting, and clinical followup. The findings were compared with the recommendations of the European Network for the Study of Adrenal Tumors (ENSAT). Results: Data were analyzed from 387 patients who had been given an initial diagnosis of ACC in the years 1998 to 2009. 21\% of them underwent no hormonal evaluation before surgery, and 59\% underwent an inadequate hormonal evaluation. This exposed the patients to unnecessary perioperative risks and impaired their follow-up. 48\% did not undergo CT scanning of the chest, even though the lungs are the most frequent site of metastases of ACC. For 13\% of the patients, the diagnosis of ACC was later revised by a reference pathologist. For 11\% of the patients, the histopathology report contained no information about resection status, even though this is an important determinant of further treatment and prognosis. Optimal management requires re-staging at three-month intervals, yet some patients underwent re-staging only after a longer delay, or not at all. Conclusion: We have identified significant deficits in the care of patients with ACC in Germany. We suspect that the situation is similar for other rare diseases. The prerequisite to better care is close and early cooperation of the treating physicians with specialized centers.},
  language  = {en}
}