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CYP2W1 Is Highly Expressed in Adrenal Glands and Is Positively Associated with the Response to Mitotane in Adrenocortical Carcinoma

Please always quote using this URN: urn:nbn:de:bvb:20-opus-113096
  • 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 byBackground 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.show moreshow less

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Metadaten
Author: Cristina L. Ronchi, Silviu Sbiera, Marco Volante, Sonja Steinhauer, Vanessa Scott-Wild, Barbara Altieri, Matthias Kroiss, Margarita Bala, Mauro Papotti, Timo Deutschbein, Massimo Terzolo, Martin Fassnacht, Bruno Allolio
URN:urn:nbn:de:bvb:20-opus-113096
Document Type:Journal article
Faculties:Medizinische Fakultät / Pathologisches Institut
Medizinische Fakultät / Medizinische Klinik und Poliklinik I
Language:English
Year of Completion:2014
Source:PLoS ONE 9(8): e105855. doi:10.1371/journal.pone.0105855
DOI:https://doi.org/10.1371/journal.pone.0105855
Sonstige beteiligte Institutionen:Comprehensive Cancer Center Mainfranken, University Hospital, University of Wuerzburg, Wuerzburg, Germany
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:CYP2W1; adrenal glands; cancer treatment; carcinomas; drug therapy; hormones; immune response; immunohistochemistry techniques; surgical oncology
Release Date:2015/05/19
Collections:Open-Access-Publikationsfonds / Förderzeitraum 2014
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung