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

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 pat...

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Bibliographic Details
Published in:Digestive diseases and sciences 2012-01, Vol.57 (1), p.72-78
Main Authors: Lee, Sun-Young, Miyai, Katsuya, Han, Hye Seung, Hwang, Dae-Yong, Seong, Moo Kyung, Chung, Heekyung, Jung, Barbara H., Devaraj, Bikash, McGuire, Kathleen L., Carethers, John M.
Format: Article
Language:English
Subjects:
Adenocarcinoma - genetics
Adenocarcinoma - pathology
Adenoma - genetics
Adenoma - pathology
Analysis
Biochemistry
CD4-CD8 Ratio
CD4-Positive T-Lymphocytes - pathology
CD8-Positive T-Lymphocytes - pathology
Cell Differentiation
Cohort Studies
Colorectal cancer
Colorectal Neoplasms - genetics
Colorectal Neoplasms - pathology
Gastroenterology
Gastrointestinal diseases
Hepatology
Humans
Immune response
Lymphocytes, Tumor-Infiltrating - pathology
Medicine
Medicine & Public Health
Microsatellite Instability
Microsatellite Repeats - genetics
Oncology
Original Article
Retrospective Studies
T cells
Transplant Surgery
Tumors
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Summary: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.
ISSN:0163-2116
1573-2568
DOI:10.1007/s10620-011-1825-5