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

• Published in: Cancer research (Chicago, Ill.) Vol. 61; no. 18; pp. 6762 - 6767
• Main Authors: GICQUEL, Christine, BERTAGNA, Xavier, PLOUIN, Pierre-Francois, LUTON, Jean-Pierre, LE BOUC, Yves, GASTON, Véronique, COSTE, Joël, LOUVEL, Albert, BAUDIN, Eric, BERTHERAT, Jérome, CHAPUIS, Yves, DUCLOS, Jean-Marc, SCHLUMBERGER, Martin
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.09.2001
• Subjects: Adolescent; Adrenal Cortex Neoplasms - genetics; Adrenal Cortex Neoplasms - metabolism; Adrenal Cortex Neoplasms - surgery; Adrenals. Adrenal axis. Renin-angiotensin system (diseases); Adult; Aged; Aged, 80 and over; Biological and medical sciences; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 17; Cohort Studies; Disease-Free Survival; Endocrinopathies; Female; Gene Expression; Humans; Insulin-Like Growth Factor II - biosynthesis; Insulin-Like Growth Factor II - genetics; Loss of Heterozygosity; Male; Malignant tumors; Medical sciences; Middle Aged; Multivariate Analysis; Neoplasm Recurrence, Local - genetics; Prospective Studies; Endocrinopathy; Human; Relapse; Prognosis; Adrenal cortex diseases; Genetic marker; Sporadic; Adrenal cortex; Malignant tumor; Chromosome C11; Insulin like growth factor 2; Chromosome E17; Cohort study; Adrenal gland diseases; Loss of heterozygosity
• ISSN: 0008-5472

Genetic alterations, such as loss of heterozygosity (LOH) at the 17p13 and 11p15 loci and overexpression of the insulin-like growth factor (IGF)-II gene, are associated with the malignant phenotype in sporadic adrenocortical tumors. 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. Reliable prognostic markers are required to identify subjects at high risk of recurrence. The aim of this study was to assess the prognostic value of three molecular markers (17p13 LOH, 11p15 LOH, and overexpression of the IGF-II gene) by assessing disease-free survival in a large series of adult patients with sporadic adrenocortical tumors. Adult patients (114) were prospectively followed up from diagnosis of the disease to June 1999 or to death. Malignancy was initially diagnosed in 18 patients (McFarlane stage III: n = 1 and stage IV: n = 17). The remaining 96 patients with localized adrenal disease at diagnosis (stage I: n = 60 and stage II: n = 36) were at risk of recurrence. Histological grade was assessed according to Weiss criteria, and tumors were classified into two groups (Weiss score <or=3 and Weiss score >or=4). Tumor samples were analyzed for LOH at the 17p13 and 11p15 loci and for IGF-II gene mRNA content. 17p13 LOH was a strong predictor of shorter disease-free survival in univariate analysis (P = 0.001; relative risk, 27), as were histological grade (Weiss score >or=4; P = 0.00001; relative risk, 15), 11p15 LOH (P = 0.004; relative risk, 9), tumor size (size >5 cm; P = 0.006; relative risk, 18), and overexpression of the IGF-II gene (P = 0.01; relative risk, 5). In a Cox proportional hazards regression model, histological grade (P = 0.04; relative risk, 4.2) and 17p13 LOH (P = 0.009; relative risk, 21.5) were independently associated with recurrence. Molecular markers, particularly 17p13 LOH, are predictive of long-term outcome in patients with sporadic adrenocortical tumors. In patients who have undergone curative surgery, routine assessment of these tumor markers is a useful complement to histological scoring for predicting recurrence and guiding decisions for subsequent follow-up and management.