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Microsatellite Instability, EMAST, and Morphology Associations with T Cell Infiltration in Colorectal Neoplasia

Digestive Diseases and Sciences volume 57, pages 72–78 (2012)Cite this article

Abstract

Background and Objectives

Colorectal tumors are often observed with tumor infiltrating lymphocytes, presumably as a host-immune response, and patterns may segregate by types of genomic instability. Microsatellite unstable (MSI) colorectal cancers contain a pronounced lymphocyte reaction that can pathologically identify these tumors. Colorectal tumors with elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) have not been examined for lymphocyte patterns.

Methods

We evaluated a 108-person cohort with 24 adenomas and 84 colorectal cancers for MSI and EMAST. Immunohistochemical detection of CD4+ and CD8+ T cell infiltration were performed. Prognostic relevance was assessed by survival analysis.

Results

CD8+ T cell infiltration in the tumor cell nest (p = 0.013) and tumor stroma (p = 0.004) were more prominent in moderately and poorly differentiated adenocarcinoma than in adenoma and well-differentiated adenocarcinoma. CD8+ T cells in the tumor cell nest (p = 0.002) and tumor stroma (p = 0.009) were at higher density in tumors with ulcerating features compared to tumors with a sessile or polypoid appearance. MSI-H tumors showed a higher density of CD8+ T cell infiltrations in tumor cell nests (p = 0.003) and tumor stroma (p = 0.001). EMAST-positive tumors showed a higher density of CD8+ T cell infiltrations than EMAST-negative tumors both in tumor cell nest (p = 0.027) and in tumor stroma (p = 0.003). These changes were not observed with CD4+ T lymphocytes. There was no difference in cancer patient survival based on density of CD8+ cells.

Conclusions

CD8+ T lymphocytes, but not CD4+ cells, were increased in tumor cell nests and the tumor stroma in both MSI and EMAST tumors, and showed higher infiltration in ulcerated tumors. CD8+ T lymphocyte infiltration is associated with both EMAST and MSI patterns, and increases with histological advancement.

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Acknowledgments

This study was supported by Konkuk University, the US Public Health Service (DK067287), the UCSD Digestive Diseases Research Development Center (DK080506), and the SDSU/UCSD Comprehensive Cancer Center Partnership (CA132379 and CA132384).

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Affiliations

  1. Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea

    Sun-Young Lee

  2. Department of Medicine and Moores Comprehensive Cancer Center, University of California, San Diego, CA, USA

    Sun-Young Lee, Heekyung Chung, Barbara H. Jung, Bikash Devaraj & John M. Carethers

  3. Department of Pathology, University of California, San Diego, CA, USA

    Katsuya Miyai

  4. Department of Pathology, Konkuk University School of Medicine, Seoul, Korea

    Hye Seung Han

  5. Department of Surgery, Konkuk University School of Medicine, Seoul, Korea

    Dae-Yong Hwang & Moo Kyung Seong

  6. Department of Biology, San Diego State University, San Diego, CA, USA

    Kathleen L. McGuire

  7. Department of Internal Medicine, University of Michigan, 1500 E. Medical Center Drive, SPC 5368, Ann Arbor, MI, 48109-5368, USA

    John M. Carethers

Authors
  1. Sun-Young Lee
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  2. Katsuya Miyai
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  3. Hye Seung Han
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  4. Dae-Yong Hwang
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  5. Moo Kyung Seong
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  6. Heekyung Chung
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  7. Barbara H. Jung
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  8. Bikash Devaraj
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  9. Kathleen L. McGuire
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  10. John M. Carethers
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Corresponding author

Correspondence to John M. Carethers.

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Lee, SY., Miyai, K., Han, H.S. et al. Microsatellite Instability, EMAST, and Morphology Associations with T Cell Infiltration in Colorectal Neoplasia. Dig Dis Sci 57, 72–78 (2012). https://doi.org/10.1007/s10620-011-1825-5

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  • DOI: https://doi.org/10.1007/s10620-011-1825-5

Keywords

  • Colorectal cancer
  • Adenoma
  • T lymphocyte
  • Microsatellite instability
  • Elevated microsatellite alterations at selected tetranucleotide repeats (EMAST)