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      Clinical implication of HLA class I expression in breast cancer

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          Abstract

          Background

          Human leukocyte antigen (HLA)-class I molecules on tumor cells have been regarded as crucial sites where cytotoxic T lymphocytes (CTL) can recognize tumor-specific antigens and are strongly associated with anti-tumor activity. However, the clinical impact of HLA class I expression in breast cancer has not been clarified.

          Methods

          A total of 212 breast cancer patients who received curative surgery from 1993 to 2003 were enrolled in the current study. HLA class I expression was examined immunohistochemically using an anti-HLA class I monoclonal antibody. The correlation between HLA class I positivity and clinical factors was analyzed.

          Results

          The downregulation of HLA class I expression in breast cancer was observed in 69 patients (32.5%). HLA class I downregulation was significantly associated with nodal involvement (p < 0.05), TNM stage (p < 0.05), lymphatic invasion (p < 0.01), and venous invasion (p < 0.05). Patients with preserved HLA class I had significantly better disease-free interval (DFI) than those with loss of HLA class I (p < 0.05). However, in multivariable analysis, HLA class I was not selected as one of the independent prognostic factors of disease-free interval.

          Conclusion

          The examination of HLA class I expression is useful for the prediction of tumor progression and recurrent risk of breast cancer via the antitumor immune system.

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          Most cited references26

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          Escape of human solid tumors from T-cell recognition: molecular mechanisms and functional significance.

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            Implications for immunosurveillance of altered HLA class I phenotypes in human tumours.

            HLA class I downregulation is a frequent event associated with tumour invasion and development. Altered HLA class I tumour phenotypes can have profound effects on T-cell and natural killer (NK)-cell antitumour responses. Here, Federico Garrido and colleagues analyse these altered tumour phenotypes in detail, indicating their potential relevance for implementation of immunotherapeutic protocols and strategies to overcome tumour escape mechanisms.
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              HLA-E and HLA-G expression in classical HLA class I-negative tumors is of prognostic value for clinical outcome of early breast cancer patients.

              Nonclassical HLAs, HLA-E and HLA-G, are known to affect clinical outcome in various tumor types. We examined the clinical impact of HLA-E and HLA-G expression in early breast cancer patients, and related the results to tumor expression of classical HLA class I. Our study population (n = 677) consisted of all early breast cancer patients primarily treated with surgery in our center between 1985 and 1995. Tissue microarray sections of arrayed tumor and normal control material were immunohistochemically stained for HLA-E and HLA-G. For evaluation of HLA-E and HLA-G and the combined variable, HLA-EG, a binary score was used. Expression of classical HLA class I molecules was determined previously. HLA-E, HLA-G, and HLA-EG on breast tumors were classified as expression in 50, 60, and 23% of patients, respectively. Remarkably, only in patients with loss of classical HLA class I tumor expression, expression of HLA-E (p = 0.027), HLA-G (p = 0.035), or HLA-EG (p = 0.001) resulted in a worse relapse-free period. An interaction was found between classical and nonclassical HLA class I expression (p = 0.002), suggestive for a biological connection. We have demonstrated that, next to expression of classical HLA class I, expression of HLA-E and HLA-G is an important factor in the prediction of outcome of breast cancer patients. These results provide further evidence that breast cancer is immunogenic, but also capable of evading tumor eradication by the host's immune system, by up- or downregulation of HLA class Ia and class Ib loci.
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                Author and article information

                Journal
                BMC Cancer
                BMC Cancer
                BioMed Central
                1471-2407
                2011
                20 October 2011
                : 11
                : 454
                Affiliations
                [1 ]Department of Surgical Oncology, Breast and Endocrine Surgery, Kagoshima University School of Medicine, Kagoshima, Japan
                [2 ]Department of Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
                Article
                1471-2407-11-454
                10.1186/1471-2407-11-454
                3214195
                22014037
                79936a13-90a3-49f0-aa01-0e8b0226d1c0
                Copyright ©2011 Kaneko et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 10 January 2011
                : 20 October 2011
                Categories
                Research Article

                Oncology & Radiotherapy
                t cell immunology,antitumor activity,hla class i,survival
                Oncology & Radiotherapy
                t cell immunology, antitumor activity, hla class i, survival

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