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The Prognostic Value of Tumor-Infiltrating lymphocytes in Stage II Colon Cancer. A Nationwide Population-Based Study
Authors:Ann C. Eriksen  Flemming B. Sørensen  Jan Lindebjerg  Henrik Hager  René dePont Christensen  Sanne Kjær-Frifeldt  Torben F. Hansen
Affiliation:2. Institute of Regional Health Research, University of Southern Denmark, Winsløvparken 19, DK-5000, Odense C, Denmark;3. University Institute of Pathology, Aarhus University Hospital, Tage-Hansens Gade 2, DK-8000 Aarhus C, Denmark;4. Research Unit of General Practice, J.B. Winsløvs Vej 9A, DK-5000 Odense C, Denmark;5. Danish Colorectal Cancer Group (DCCG)
Abstract:BACKGROUND: Additional prognostic markers are needed for better treatment stratification of stage II colon cancer (CC). We investigated the prognostic value of tumor-infiltrating lymphocytes (TILs) in a true population-based cohort of patients with stage II CC. MATERIAL AND METHODS: A total of 573 patients were included. Tumor blocks representing the deepest invasive part of the primary tumor were used for analysis. CD3+ and CD8+ TILs at the invasive front were evaluated by immunohistochemistry on whole tumor sections. The invasive area was manually outlined, and Visiopharm Integrator System software was used for quantification. Data were dichotomized for comparison with clinical data. The prognostic value was investigated in Cox proportional-hazard models for recurrence-free survival (RFS) and overall survival (OS). RESULTS: Low CD3+ or CD8+ TILs were significantly associated with poor RFS and OS (P?=?.0021 and P?≤?.0009, respectively, log-rank test). In multiple Cox regression analysis, low CD3+ and CD8+ TILs were associated with reduced RFS with hazard ratio (HR)?=?1.386 (95% CI 1.039-1.850), P?=?.026, and HR?=?1.394 (95% CI 1.029-1.890), P?=?.032, respectively, independent of age, T-stage, localization, perforation, and microsatellite instability (MSI). In the subgroups of patients with low CD3+ or CD8+ TILs, there was no difference in survival between patients with MSI and microsatellite-stable tumors, (P?=?.821 and P?=?.907, respectively). CONCLUSION: Low CD3+ and CD8+ TILs in the invasive area are both related to inferior prognosis of stage II CC, and we recommend either of these parameters to be considered as additional high-risk factor.
Keywords:Address all correspondence to: Ann Christina Eriksen   MD   PhD student   Department of Pathology   Vejle Hospital   Beriderbakken 4   DK-7100 Vejle   Denmark.
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