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This version published online on December 7, 2004
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2004-1406
A more recent version of this article appeared on March 1, 2005
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Submitted on July 23, 2004
Accepted on December 1, 2004

PREVALENCE OF HLA-DRB1 GENOTYPE AND ALTERED FAS/FAS-L EXPRESSION IN ADRENOCORTICAL CARCINOMA

Gernot W. Wolkersdörfer*, Christian Marx, John Brown, Sabine Schröder, Monika, Füssel, E. Peter Rieber, Eberhard Kuhlisch, Gerhard Ehninger, and Stefan R. Bornstein

Department of Internal Medicine I, Technical University of Dresden, Germany; Veteran Affairs Medical Center, Miami, Florida 33149, U.S.A.; Department of Immunology, University of Leipzig, Germany, Department of Immunology, Technical University of Dresden, Germany; IMIB, Technical University of Dresden, Germany; Department of Endocrinology, Heinrich Heine University, Düsseldorf, Germany

* To whom correspondence should be addressed. E-mail: wolkersdoerfer{at}mk1.med.tu-dresden.de.

A distinctive feature of malignant adrenocortical neoplasms is decreased 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-L 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), while 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. Further 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 suggests new diagnostic approaches.




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S. R. Bornstein and P. J. Hornsby
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