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HLA-A2 expression, stage, and survival in colorectal cancer

  • Original Article
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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Introduction

Most cancer vaccination trials have been performed in human leukocyte antigen (HLA)-A2 positive populations. Some studies have used HLA-A2 negative patients as control group. However, HLA-type and HLA-expression can interact with tumor biology and possibly affect prognosis. HLA-A2 negative patients might constitute an inadequate control group.

Materials and methods

Patients with colorectal cancer were serologically analyzed for HLA-A2 expression. Patients were evaluated for tumor stage, grading, tumor location. Overall survival (OAS) of HLA-A2 positive and HLA-A2 negative patients was compared.

Results

One hundred forty-four patients were evaluable (50% HLA-A2+). Median age was 62 years. UICC stage III or IV: 45.8%. Gender, location, and UICC stage were equally distributed between HLA-A2 subgroups. HLA-A2 positive patients more frequently had grade 3 histology (27.8% vs 13.9%) and chemotherapy (62.9% vs 45.6%). At a median follow-up of 75.8 months, median OAS for the entire study population was 123.3 months, 5-year OAS was 77.5%. No statistically significant difference in OAS was observed between HLA-A2 positive and negative patients (116.5 vs 157 months, 5-year-OAS 74.1 ± 11.6% vs 81 ± 11.6%, p = 0.46). Expectedly, patients with UICC stage I and II disease lived significantly longer than patients with stage III and IV (5-year OAS 94.3% vs 53.4%; p < 0.001). A significantly superior OAS was also found for women, independent of stage or HLA status.

Conclusion

HLA-A2 positive patients exhibit poorer tumor differentiation. This might account for a non-significant difference in OAS. The use of HLA-A2 negative patients as control cohort in CRC vaccinations would rather underestimate potential treatment-related survival effects. Therefore, we suggest they constitute a valid auxiliary control group.

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Abbreviations

CRC:

colorectal cancer

DC:

dendritic cells

HLA:

human leukocyte antigen

TAA:

tumor associated antigen

NPC:

nasopharyngeal carcinoma

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Acknowledgments

We thank Sandra Bauer, Susanne Wojtke, and the whole HLA-Lab team (particularly, Kristina Zuber, Nora Wendt, Sabrina Ballaschke, Kerstin Thomas) for excellent technical assistance.

This work was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG NA 716/1-1).

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Author notes

  1. Dirk Nagorsen

    Present address: Micromet AG, Staffelseestr. 2, 81477, München, Germany

Authors and Affiliations

  1. Department of Hematology and Oncology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany

    Philipp Kiewe, Veit Mansmann, Eckhard Thiel & Dirk Nagorsen

  2. Department of Medical Immunology, Charité-Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany

    Carmen Scheibenbogen

  3. Department of Surgery, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany

    Heinz-Johannes Buhr

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  1. Philipp Kiewe
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Correspondence to Dirk Nagorsen.

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Kiewe, P., Mansmann, V., Scheibenbogen, C. et al. HLA-A2 expression, stage, and survival in colorectal cancer. Int J Colorectal Dis 23, 767–772 (2008). https://doi.org/10.1007/s00384-008-0488-y

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