Genetic alterations of HLA-class II in ovarian cancer.
The immune system controls tumor formation through identification and elimination of cellular alterations. Consequently, cancer development in immune competent hosts depends on strategies to evade the immune system. Modulation of tumor antigen-specific immune responses by aberrant expression of HLA-class I and II molecules is well documented in a variety of carcinomas including ovarian cancer. To date, little data are available about molecular mechanisms responsible for altered HLA-class II phenotypes in tumors. In our sample of 10 Caucasian patients with ovarian carcinoma, a semiquantitative analysis was performed for HLA-class II loci DRB1 and DQB1 in malignant and normal ovarian tissue. Gene amplifications were identified in 62.5% of analyzed alleles and deletions in 17.5%, demonstrating that genomic aberrations of 6p21.3 are common and that copy number gain is more frequent than loss. Moreover, amplifications are most pronounced in advanced-stage tumors. To evaluate genotype-phenotype relation, immunohistochemical analyses were performed and revealed de novo expression of HLA-class II in 30% of tumors with an inverse association between antigen level and HLA copy number. It remains to be elucidated whether the profound changes of the latter quantities are the result of the host's immunological self-defense, indicate the presence of an oncogene located within the MHC-complex or merely reflect the increasing loss of differentiation of the tumor tissue.
Department of Obstetrics and Gynecology, University of Bonn, Sigmund Freud Strasse 25, 53127 Bonn, Germany.
Kirsten
K
Kübler
Peter F
PF
Arndt
Eva
E
Wardelmann
Christina
C
Landwehr
Dieter
D
Krebs
Walther
W
Kuhn
Katrin
K
van der Ven
D000328:Adult; D000368:Aged; D005260:Female; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction
D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains