title: Microsatellite instability, EMAST, and morphology associations with T cell infiltration in colorectal neoplasia.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Katsuya
authors.initials: K
authors.lastname: Miyai
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Han
authors.forename: Dae-Yong
authors.initials: DY
authors.lastname: Hwang
authors.forename: Moo Kyung
authors.initials: MK
authors.lastname: Seong
authors.forename: Heekyung
authors.initials: H
authors.lastname: Chung
authors.forename: Barbara H
authors.initials: BH
authors.lastname: Jung
authors.forename: Bikash
authors.initials: B
authors.lastname: Devaraj
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: McGuire
authors.forename: John M
authors.initials: JM
authors.lastname: Carethers
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000236:Adenoma / Q000235:genetics / Q000473:pathology; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D002454:Cell Differentiation; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology*; D053842:Microsatellite Instability; D018895:Microsatellite Repeats / Q000235:genetics*; D012189:Retrospective Studies