Prevalence of HLA-DRB1 Genotype and Altered Fas/Fas Ligand Expression in Adrenocortical Carcinoma

• Published in: The journal of clinical endocrinology and metabolism 2005-03, Vol.90 (3), p.1768-1774
• Main Authors: Wolkersdörfer, Gernot W., Marx, Christian, Brown, John, Schröder, Sabine, Füssel, Monika, Rieber, E. Peter, Kuhlisch, Eberhard, Ehninger, Gerhard, Bornstein, Stefan R.
• Format: Article
• Language: English
• Subjects: Adolescent; Adrenal Cortex Neoplasms - epidemiology; Adrenal Cortex Neoplasms - genetics; Adrenal Cortex Neoplasms - metabolism; Adrenals. Adrenal axis. Renin-angiotensin system (diseases); Adrenocortical Carcinoma - epidemiology; Adrenocortical Carcinoma - genetics; Adrenocortical Carcinoma - metabolism; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Child; Child, Preschool; Endocrinopathies; Fas Ligand Protein; fas Receptor - metabolism; Female; Fundamental and applied biological sciences. Psychology; Genetic Predisposition to Disease - epidemiology; Genotype; HLA-DR Antigens - genetics; HLA-DRB1 Chains; Humans; Immunohistochemistry; Male; Malignant tumors; Medical sciences; Membrane Glycoproteins - metabolism; Middle Aged; Prevalence; Risk Factors; Vertebrates: endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2004-1406

A distinctive feature of malignant adrenocortical neoplasms is decreased major histocompatibility complex (MHC) class II molecule expression. However, it is unknown whether there exists a restriction to certain MHC genotypes and whether this involves alterations of the Fas/Fas ligand system and thereby affects tissue homeostasis. Therefore, MHC class II phenotype and genotype and expression patterns of the Fas/Fas ligand system were investigated in 24 adrenocortical tumors (nAdenomas = 14, nCarcinomas = 10) and an adrenal cancer cell line (NCI-H295). No MHC class II antigen expression was detected in carcinomas. The DRB1*01 genotype was found in 54.5% of patients with carcinoma (P = 0.046). No prevalence of any genotype could be detected in patients with adenomas, which exhibited varying levels of antigen expression. Fas receptor expression was 75.0% in adenomas compared with 20.0% in carcinomas (P = 0.0196), whereas ligand expression was 37.7% in adenomas and reached almost 100% in the carcinomas investigated in this study (P = 0.0033). In summary, the DRB1*01 genotype may be correlated to a higher risk for malignancy. Additional studies on MHC class II genotype and phenotype and the altered Fas/Fas ligand system in adrenal neoplasms may help to identify mechanisms of immune escape and suggest new diagnostic approaches.