Prevalence of HLA-DRB1 genotype and altered Fas/Fas ligand expression in adrenocortical carcinoma.
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.
Wolkersdörfer
Gernot W
GW
Medical Department I, Faculty of Medicine Carl Gustav Carus, University of Technology Dresden, Fetscherstrasse 74, Dresden 01307, Germany. wolkersdoerfer@mk1.med.tu-dresden.de
Marx
Christian
C
Brown
John
J
Schröder
Sabine
S
Füssel
Monika
M
Rieber
E Peter
EP
Kuhlisch
Eberhard
E
Ehninger
Gerhard
G
Bornstein
Stefan R
SR
D000293:Adolescent; D000306:Adrenal Cortex Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D018268:Adrenocortical Carcinoma / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D053222:Fas Ligand Protein; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D015995:Prevalence; D012307:Risk Factors; D019014:fas Receptor / Q000378:metabolism*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D008562:Membrane Glycoproteins; D019014:fas Receptor