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

Departments of Internal Medicine I (G.W.W., C.M., G.E.), Internal Medicine III (S.R.B.), and Immunology (M.F., E.P.R.) and Institute of Medical Informatics and Biometry (E.K.), University of Technology Dresden, Dresden 01307, Germany; Veteran Affairs Medical Center (J.B.), Miami, Florida 33149; and Department of Immunology (S.S.), University of Leipzig, Leipzig 04129, Germany

Address all correspondence and requests for reprints to: Gernot W. Wolkersdörfer, Medical Department I, Faculty of Medicine Carl Gustav Carus, University of Technology Dresden, Fetscherstrasse 74, Dresden 01307, Germany. E-mail: wolkersdoerfer{at}mk1.med.tu-dresden.de.

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 (n_Adenomas = 14, n_Carcinomas = 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.

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