title: Image analyzer-based assessment of tumor-infiltrating T cell subsets and their prognostic values in colorectal carcinomas.
abstract: To find useful tools to evaluate the prognosis in colorectal carcinoma (CRC) patients, we investigated the prognostic values of tumor-infiltrating T lymphocyte subsets according to intratumoral subsites as well as clinical or molecular characteristics. Immunohistochemistry for CD8, CD45RO, and FOXP3 was performed, and densities of the T cell subsets in each tissue microarray core (cells/mm2) were measured by image analysis. In the training set (n = 218) of CRC, T cell subset densities in the invasion front were more strongly associated with patient outcome than those in the tumor center. In the validation set (n = 549), T cell subset densities in the invasion front were evaluated. Univariate analysis showed that all three T cell subset densities were significantly associated with longer progression free survival and overall survival time (p < 0.001). In multivariate analysis, a high CD45RO density correlated independently with longer progression free survival (p = 0.011) and overall survival time (p = 0.007) in CRC patients, regardless of tumor location or adjuvant chemotherapy status. Our results showed that CD45RO density in the invasion front was the only independent prognostic factor regarding CRC. However, CD8 and FOXP3 densities were also independent prognostic factors in certain clinical settings. Thus, image analysis of tissue microarray cores in the invasion front of CRC could be used as a valid method for evaluating the prognostic significance of T cell subset densities.
authors: Department of Pathology, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea.
authors: Younghoon
authors: Y
authors: Kim
authors: Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea.
authors: Jeong Mo
authors: JM
authors: Bae
authors: Department of Pathology, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea.
authors: Gang
authors: G
authors: Li
authors: Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea.
authors: Nam Yun
authors: NY
authors: Cho
authors: Department of Pathology, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea; Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea.
authors: Gyeong Hoon
authors: GH
authors: Kang
mesh_terms: D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002452:Cell Count; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000302:isolation & purification; D006801:Humans; D017493:Leukocyte Common Antigens / Q000096:biosynthesis / Q000302:isolation & purification; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D057054:Molecular Imaging; D011379:Prognosis; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D046888:Tissue Array Analysis
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D017493:Leukocyte Common Antigens