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Is downregulation of MHC class I antigen expression in human non-small cell lung cancer associated with prolonged survival?

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Abstract

Purpose: To characterize HLA class I antigen expression in non-small cell lung cancer (NSCLC) lesions, and to assess the clinical significance of these molecules’ downregulation. Methods: One hundred and ninety primary formalin fixed, paraffin embedded NSCLC lesions were stained with HLA class I heavy chain-specific mAb HC-10. Results were scored as percentage of stained tumor cells and categorized into three groups: 0–24% (negative), 25–75% (heterogeneous) and >75% (positive). HLA class I antigen expression was correlated with clinical and pathologic predictors of time to progression and survival and analyzed using the chi-square test. Association between HLA class I antigen expression and survival was assessed using Cox regression models, while controlling for confounders. Results: HLA class I antigen expression was negative, heterogeneous and positive in 153, 25 and 12 primary NSCLC lesions, respectively. Independent variables significantly associated with survival included tumor stage, PS and weight loss. The median survival times were 40.6, 44.0 and 17.9 months for patients with a HLA class I antigen expression scored as negative, heterogeneous and positive, respectively. Conclusion: HLA class I antigen defects were found with high frequency (93.6%) in NSCLC lesions. HLA class I antigen downregulation was associated with improved survival, although this association was not statistically significant. These results, which parallel similar findings in uveal melanoma and in breast carcinoma, raise the possibility that NK cells may play a role in the control of NSCLC tumors.

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Acknowledgements

We thank Joan Beck for her assistance in the preparation and processing of tumor procurement and Debbie Malik for her expert assistance in histology

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Authors and Affiliations

  1. Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA

    N. Ramnath

  2. Department of Pathology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA

    P. Bogner

  3. Department of Biostatistics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA

    Q. Li

  4. Department of Immunology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA

    B. L. Hylander, L. Ryes & S. Ferrone

  5. Department of Pathology & Laboratory Medicine, University of Texas Medical Center, Houston, TX, 77030, USA

    D. Tan

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  1. N. Ramnath
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  2. D. Tan
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  3. Q. Li
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  4. B. L. Hylander
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  6. L. Ryes
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  7. S. Ferrone
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Correspondence to N. Ramnath.

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N. Ramnath and D. Tan contributed equally to the paper

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Ramnath, N., Tan, D., Li, Q. et al. Is downregulation of MHC class I antigen expression in human non-small cell lung cancer associated with prolonged survival?. Cancer Immunol Immunother 55, 891–899 (2006). https://doi.org/10.1007/s00262-005-0085-7

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  • DOI: https://doi.org/10.1007/s00262-005-0085-7

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