Molecular analysis of CDKN1C and TP53 in sporadic adrenal tumors

Objective: To evaluate the roles of the CDKN1C (P57KIP2) gene, which encode s for the cyclin-dependent kinase inhibitor CDNC, and the TP53 tumor suppre ssor gene in adrenal tumorigenesis, as a means of investigating the molecul ar basis of sporadic adrenal tumors, which is unknown. Design: Screening for the presence CDKN1C and TP53 mutations and analyzing the expression pattern of CDNC. P53 and its downstream effector CDN1 (P21WA F1/CIP1) in a series of 79 sporadic adrenal tumors. Methods: Single-strand conformation polymorphism and sequencing were used f or mutation analysis of CDKN1C and TP53 in blood and adrenal tissue samples . In a subgroup of 48 tissues, CDKN1C expression was evaluated by RT-PCR an d immunohistochemistry. Immunohistochemical analysis of P53 and CDN1 was pe rformed. Results: No somatic mutations of CDKN1C were found in the tumors analyzed, in spite of low/absent CDNC expression in adrenocortical adenomas and carci nomas. Mutations in the TP53 gene were present in 70% of adrenocortical car cinomas, associated with abnormal P53 and CDN1 expression, but not in benig n neoplasms. In the normal adrenal cortex. CDNC expression was strictly nuc lear and confined to the cortical zone (i.e. zona glomerulosa and reticular is), with no staining in the medulla. Conclusions: Mutations in the TP53 gene are frequent in adrenocortical carc inomas and might be used as a marker of malignancy. In the normal adrenal c ortex, the zone-specific pattern of expression of CDNC suggests a role in a drenal differentiation.