HLA class I antigen down-regulation in primary ovary carcinoma lesions: association with disease stage
- PMID: 15671529
HLA class I antigen down-regulation in primary ovary carcinoma lesions: association with disease stage
Abstract
Purpose: 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.
Experimental design: 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.
Similar articles
-
Association of tapasin and HLA class I antigen down-regulation in primary maxillary sinus squamous cell carcinoma lesions with reduced survival of patients.Clin Cancer Res. 2003 Sep 15;9(11):4043-51. Clin Cancer Res. 2003. PMID: 14519625
-
HLA class I antigen down-regulation in primary laryngeal squamous cell carcinoma lesions as a poor prognostic marker.Cancer Res. 2006 Sep 15;66(18):9281-9. doi: 10.1158/0008-5472.CAN-06-0488. Cancer Res. 2006. PMID: 16982773
-
Human leukocyte antigen class I antigen expression is an independent prognostic factor in ovarian cancer.Clin Cancer Res. 2007 Jun 15;13(12):3591-6. doi: 10.1158/1078-0432.CCR-06-2087. Clin Cancer Res. 2007. PMID: 17575223
-
HLA class I antigen expression in malignant cells: why does it not always correlate with CTL-mediated lysis?Curr Opin Immunol. 2004 Oct;16(5):644-50. doi: 10.1016/j.coi.2004.07.015. Curr Opin Immunol. 2004. PMID: 15342012 Review.
-
Downregulation of tapasin expression in progressive human malignant melanoma.Arch Dermatol Res. 2003 Jun;295(2):43-9. doi: 10.1007/s00403-003-0393-8. Epub 2003 Mar 28. Arch Dermatol Res. 2003. PMID: 12682852 Review.
Cited by
-
Spectrum of HLA associations: the case of medically refractory pediatric acute lymphoblastic leukemia.Immunogenetics. 2012 Jun;64(6):409-19. doi: 10.1007/s00251-012-0605-5. Epub 2012 Feb 15. Immunogenetics. 2012. PMID: 22350167 Free PMC article.
-
In vivo expression of MHC class I genes depends on the presence of a downstream barrier element.PLoS One. 2009 Aug 26;4(8):e6748. doi: 10.1371/journal.pone.0006748. PLoS One. 2009. PMID: 19707598 Free PMC article.
-
Molecular mechanisms of MHC class I abnormalities and APM components in human tumors.Cancer Immunol Immunother. 2008 Nov;57(11):1719-26. doi: 10.1007/s00262-008-0515-4. Epub 2008 Apr 12. Cancer Immunol Immunother. 2008. PMID: 18408926 Free PMC article. Review.
-
c-Myc and EBV-LMP1: two opposing regulators of the HLA class I antigen presentation machinery in epithelial cells.Br J Cancer. 2012 Jun 5;106(12):1980-8. doi: 10.1038/bjc.2012.197. Epub 2012 May 15. Br J Cancer. 2012. PMID: 22588558 Free PMC article.
-
Immunologic aspect of ovarian cancer and p53 as tumor antigen.J Transl Med. 2005 Sep 15;3:34. doi: 10.1186/1479-5876-3-34. J Transl Med. 2005. PMID: 16164749 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Medical
Research Materials
Miscellaneous