Molecular markers and long-term recurrences in a large cohort of patients with sporadic adrenocortical tumors

Genetic alterations, such as loss of heterozygosity (LOH) at the 17p13 and 11p15 loci and overexpression of the insulin-like growth factor (IGF)11 gen e, are associated with the malignant phenotype in sporadic adrenocortical t umors. A high risk of recurrence after surgery for adrenocortical tumors is predicted in cases with regional invasion or distant metastases. However, patients with localized tumors also have a high risk of recurrence. Reliabl e prognostic markers are required to identify subjects at high risk of recu rrence. The aim of this study was to assess the prognostic value of three m olecular markers (17p13 LOH, 11p15 LOH, and overexpression of the IGF-H gen e) by assessing disease-free survival in a large series of adult patients w ith sporadic adrenocortical tumors. Adult patients (114) were prospectively followed up from diagnosis of the d isease to June 1999 or to death. Malignancy was initially diagnosed in 18 p atients (McFarlane stage III: n = 1 and stage IV: n = 17). The remaining 96 patients with localized adrenal disease at diagnosis (stage 1: n = 60 and stage 11: n = 36) were at risk of recurrence. Histological grade was assess ed according to Weiss criteria, and tumors were classified into two groups (Weiss score less than or equal to3 and Weiss score greater than or equal t o4). Tumor samples were analyzed for LOH at the 17p13 and 11p15 loci and fo r IGF-11 gene mRNA content. 17p13 LOH was a strong predictor of shorter disease-free survival in univar iate analysis (P = 0.001; relative risk, 27), as were histological grade (W eiss score greater than or equal to4; P = 0.00001; relative risk, 15), 11p1 5 LOH (P = 0.004; relative risk, 9), tumor size (size >5 cm; P = 0.006, rel ative risk, 18), and overexpression of the IGF-11 gene (P = 0.01; relative risk. 5). In a Cox proportional hazards regression model, histological grad e (P = 0.04; relative risk, 4.2) and 17p13 LOH (P = 0.009; relative risk, 2 1.5) were independently associated with recurrence. Molecular markers, particularly 17p13 LOH, are predictive of longterm outco me in patients with sporadic adrenocortical tumors. In patients who have un dergone curative surgery, routine assessment of these tumor markers is a us eful complement to histological scoring for predicting recurrence and guidi ng decisions for subsequent follow-up and management.