Exp Clin Endocrinol Diabetes 2014; 122 - OP5_24
DOI: 10.1055/s-0034-1371999

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

CL Ronchi 1, S Sbiera 1, 2, M Volante 3, S Steinhauer 1, V Wild-Scott 4, M Kroiss 1, M Papotti 5, T Deutschbein 1, M Terzolo 6, M Fassnacht 1, 2, B Allolio 1
  • 1University Hospital Wuerzburg, Endocrine and Diabetes Unit, Wuerzburg, Germany
  • 2University Hospital Munich, Munich, Germany
  • 3University Turin, Department of Oncology, Turin, Italy
  • 4University Wuerzburg, Institute of Pathology, Wuerzburg, Germany
  • 5University Turin, Division of Pathology, Turin, Italy
  • 6University Turin, Division of Internal Medicine I, Turin, Italy

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.