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Relationship between HLA class I antigen processing machinery component expression and the clinicopathologic characteristics of bladder carcinomas

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Abstract

Purpose

The goal of this study was to analyze protein expression of antigen processing machinery (APM) components in bladder carcinoma (BC), and to assess the clinical significance of defects in their expression.

Experimental design

Tissue from 167 cystectomies for primary BC was used to create a tissue microarray. 128 tumors were urothelial carcinoma (UC). Immunohistochemistry was performed using 14 monoclonal antibodies to APM components (β2-microglobulin, calnexin, calreticulin, delta, Z, MB1, LMP2, LMP7, LMP10, HLA class I heavy chain, tapasin, TAP1, TAP2 and ERp57) and MHC class I-related antigen (MICA). Sections of normal urothelium from six subjects were used as controls.

Results

All APM components except MB1, LMP2 and TAP2 had significantly lower staining in UC than in normal urothelium. No significant differences were found in APM component scores between different grades of UC. Squamous cell carcinoma had the highest scores, with UC intermediate and other types of BC lowest. High-stage UC demonstrated significantly lower staining for calnexin, LMP2, LMP7 and LMP10 than low-stage UC. With mean 3.6 years follow up, significantly worse survival was associated with a higher delta score in UC (P = 0.038) and a lower calreticulin score in all tumor types (P = 0.028).

Conclusions

Most APM components were downregulated in UC. High-stage UC had lower scores for immunoproteasome components compared to low-stage UC. Delta and calreticulin protein expression was associated with survival in UC and in all types of BC, respectively. These findings suggest that APM defects play a role in the clinical course of BC and should be considered in developing immunotherapeutic approaches for its control.

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Acknowledgments

Paul Mellon Urologic Cancer Institute, University of Virginia Health System, Charlottesville, VA, and PHS Grants R01CA110249 and R01CA113861, and P01CA109688 awarded by the National Cancer Institute, DHHS.

Conflict of interest statement

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology, University of Virginia Health System, PO Box 800214, Charlottesville, VA, 22908, USA

    Helen P. Cathro, Vickie Y. Jo & Henry F. Frierson Jr.

  2. Department of Public Health Sciences, University of Virginia Health System, Charlottesville, VA, USA

    Mark E. Smolkin

  3. Departments of Urology, Molecular Physiology and Biological Physics, University of Virginia Health System, Charlottesville, VA, USA

    Dan Theodorescu

  4. Departments of Surgery, Immunology and Pathology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA

    Soldano Ferrone

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  1. Helen P. Cathro
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Correspondence to Helen P. Cathro.

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Cathro, H.P., Smolkin, M.E., Theodorescu, D. et al. Relationship between HLA class I antigen processing machinery component expression and the clinicopathologic characteristics of bladder carcinomas. Cancer Immunol Immunother 59, 465–472 (2010). https://doi.org/10.1007/s00262-009-0765-9

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  • DOI: https://doi.org/10.1007/s00262-009-0765-9

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