HLA class I antigen down-regulation in primary ovary carcinoma lesions: association with disease stage.
OBJECTIVE
To investigate TAP1, TAP2, and HLA class I antigen expression in primary ovarian carcinoma lesions and to assess the clinical significance of defects in the expression of these molecules.


METHODS
Fifty-one formalin-fixed, paraffin-embedded primary ovarian carcinoma lesions were stained with affinity-purified rabbit anti-TAP1 and anti-TAP2 antibodies and with anti-HLA class I heavy chain monoclonal antibody (mAb) HC-10 using the immunoperoxidase reaction. The results of immunohistochemical staining were correlated with the histopathologic characteristics of the lesions and with patients' survival.


RESULTS
Ovarian surface epithelium, thecal cells of follicles, and stromal cells were stained by anti-TAP1, anti-TAP2, and anti-HLA class I antigen xenoantibodies with a homogeneous pattern. In contrast, no staining of lutheinic cells by these antibodies was detected. Forty-one and 32 out of 51 primary ovarian carcinoma lesions were stained by anti-TAP1 and anti-TAP2 xenoantibodies and by anti-HLA class I antigen mAb HC-10, respectively. The staining patterns by anti-TAP1 and anti-TAP2 xenoantibodies were completely concordant, but did not correlate with that by anti-HLA class I heavy chain mAb HC-10. TAP1 and TAP2 expression was associated neither with the histopathologic characteristics of the lesions nor with clinical variables. On the other hand, HLA class I antigen down-regulation was associated with disease stage: the odds ratio of stage III for HLA class I antigen negative patients was 7.6 (95% confidence interval, 1.9-30.5; P= 0.007), whereas for TAP negative patients was 5.1 (95% confidence interval, 0.9-28.4; P = 0.07). Follow up was available for 39 out of the 51 patients. Multivariate analysis showed that both grading and staging were associated with a higher risk of death, whereas TAP and HLA class I antigen phenotypes were not.


CONCLUSIONS
The lack of association between TAP and HLA class I antigen expression is compatible with the possibility that multiple mechanisms underlie HLA class I antigen down-regulation in primary ovarian carcinoma lesions. The potential role of immunologic events in the clinical course of ovarian carcinoma suggests that the association between HLA class I antigen down-regulation and disease progression may reflect the escape of tumor cells from immune recognition and destruction.
Vitale
Marco
M
Department of Anatomy, Pharmacology and Forensic Medicine, University of Parma, Italy.
Pelusi
Giuseppe
G
Taroni
Beatrice
B
Gobbi
Giuliana
G
Micheloni
Cristina
C
Rezzani
Rita
R
Donato
Francesco
F
Wang
Xinhui
X
Ferrone
Soldano
S
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000737:chemistry; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000378:metabolism; D045744:Cell Line, Tumor; D018450:Disease Progression; D015536:Down-Regulation; D004847:Epithelial Cells / Q000166:cytology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000378:metabolism*; D010053:Ovary / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D013997:Time Factors
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D015395:Histocompatibility Antigens Class I