Digestive Diseases and Sciences

, Volume 57, Issue 1, pp 72–78

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

Authors

  • Sun-Young Lee
    • Department of Internal MedicineKonkuk University School of Medicine
    • Department of Medicine and Moores Comprehensive Cancer CenterUniversity of California
  • Katsuya Miyai
    • Department of PathologyUniversity of California
  • Hye Seung Han
    • Department of PathologyKonkuk University School of Medicine
  • Dae-Yong Hwang
    • Department of SurgeryKonkuk University School of Medicine
  • Moo Kyung Seong
    • Department of SurgeryKonkuk University School of Medicine
  • Heekyung Chung
    • Department of Medicine and Moores Comprehensive Cancer CenterUniversity of California
  • Barbara H. Jung
    • Department of Medicine and Moores Comprehensive Cancer CenterUniversity of California
  • Bikash Devaraj
    • Department of Medicine and Moores Comprehensive Cancer CenterUniversity of California
  • Kathleen L. McGuire
    • Department of BiologySan Diego State University
    • Department of Medicine and Moores Comprehensive Cancer CenterUniversity of California
    • Department of Internal MedicineUniversity of Michigan
Original Article

DOI: 10.1007/s10620-011-1825-5

Cite this article as:
Lee, S., Miyai, K., Han, H.S. et al. Dig Dis Sci (2012) 57: 72. doi:10.1007/s10620-011-1825-5

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.

Keywords

Colorectal cancerAdenomaT lymphocyteMicrosatellite instabilityElevated microsatellite alterations at selected tetranucleotide repeats (EMAST)

Copyright information

© Springer Science+Business Media, LLC 2011