Expression of CYP2W1 in the adrenal gland: relationship with hormone secretion and clinical outcome

• Published in: Experimental and Clinical Endocrinology & Diabetes
• Main Authors: Ronchi, CL, Sbiera, S, Volante, M, Steinhauer, S, Wild-Scott, V, Kroiss, M, Papotti, M, Deutschbein, T, Terzolo, M, Fassnacht, M, Allolio, B
• Format: Conference Proceeding
• Language: English
• Published: 05.03.2014
• ISSN: 0947-7349; 1439-3646
• DOI: 10.1055/s-0034-1371999

Adrenocortical tumors consist of frequent adenomas (ACA) and rare highly malignant carcinomas (ACC). The orphan enzyme cytochrome P450 2W1 (CYP2W1) is selectively expressed in some cancers and represent a promising new drug target in cancer therapy. CYP2W1 mRNA levels were analyzed in 58 frozen samples (13 normal adrenals, 17 ACA, 19 ACC, and 9 non-adrenal normal tissues). A total of 340 tissues were investigated by immunohistochemistry for CYP2W1 protein (23 normal adrenals, 29 ACA, 231 ACC, 32 non-adrenal normal tissues, and 25 non-adrenal tumors). CYP2W1 gene expression was absent in non-adrenal tissues, while it was high in both normal and neoplastic adrenal glands. At the protein level, CYP2W1 was absent/low in non-adrenal normal tissues (H-score 0 – 1 in 72% of cases), but increased in some non-adrenal cancers ( P < 0.0001 ). Again, CYP2W1 expression was high in normal adrenals (H-score 2 – 3 in 65% of cases, P < 0.0001 vs. non-adrenal normal tissues) and in adrenocortical tumors ( P NS vs. normal adrenal). CYP2W1 protein levels were higher in hormone-secreting than in non secreting tumors ( P < 0.001 for both ACA and ACC) and negatively correlated with Ki67 ( P < 0.005 ) and Weiss score ( P < 0.01 ). CYP2W1 protein expression did not influence per se the overall survival (OS, n = 190, P = 0.45 , HR = 1.17) and disease-free survival (n = 53, P = 0.44 , HR = 1.38). However, restricting the analysis to the 68 patients treated with mitotane only, there was a trend towards a longer OS in tumors with high CYP2W1 expression (median survival: 131 vs. 72 months, P = 0.17, HR = 1.63, 95% CI = 0.8 – 3.3). These findings were more evident when considering only patients with initial ENSAT stage 1 and 2 (n = 37, P = 0.045 , HR = 3.2, 95% CI = 1.0 – 10.3). In conclusion, CYP2W1 is physiologically expressed in adrenal glands, where it might play a role in steroidogenesis. High expression of CYP2W1 in ACC indicates that it might be a promising drug target. Finally, CYP2W1 may be involved in the adrenal activation of mitotane.