Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Aug;11(4):979-987.
doi: 10.1016/j.tranon.2018.03.008. Epub 2018 Jun 22.

The Prognostic Value of Tumor-Infiltrating lymphocytes in Stage II Colon Cancer. A Nationwide Population-Based Study

Ann C Eriksen  1 , Flemming B Sørensen  2 , Jan Lindebjerg  3 , Henrik Hager  4 , René dePont Christensen  5 , Sanne Kjær-Frifeldt  6 , Torben F Hansen  3
Affiliations

The Prognostic Value of Tumor-Infiltrating lymphocytes in Stage II Colon Cancer. A Nationwide Population-Based Study

Ann C Eriksen et al. Transl Oncol. 2018 Aug.

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Photomicrographs of CD3 and CD8 immunohistochemistry. The panels on the top show high cell densities, and the panels on the bottom show low densities.
Figure 2
Figure 2
Kaplan-Meier survival curves for overall survival and recurrence-free survival. (A-B) CD3+ TILs and (C-D) CD8+ TILs in the total patient population (n = 573). Invasive refers to the area of the outermost front of the adenocarcinoma, including the deepest invasive front of the tumor, areas with tumor budding, and/or irregular tumor islands.
Figure 3
Figure 3
Kaplan-Meier survival curves for recurrence-free survival for different combinations of TILs and MSI status (N = 573). (A) High CD3+ TILs versus low CD3+ TILs and (B) high CD8+ TILs versus low CD8+ TILs. Invasive refers to the area of the outermost front of the adenocarcinoma, including the deepest invasive front of the tumor, areas with tumor budding, and/or irregular tumor islands.
See this image and copyright information in PMC

References

    1. Morris M, Platell C, McCaul K, Millward M, van Hazel G, Bayliss E, Trotter J, Ransom D, Iacopetta B. Survival rates for stage II colon cancer patients treated with or without chemotherapy in a population-based setting. Int J Colorectal Dis. 2007;22:887–895. - PubMed
    1. Labianca R, Nordlinger B, Beretta GD, Mosconi S, Mandala M, Cervantes A, Arnold D. Early colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24:64–72. - PubMed
    1. Benson AB, III, Schrag D, Somerfield MR, Cohen AM, Figueredo AT, Flynn PJ, Krzyzanowska MK, Maroun J, McAllister P, Van Cutsem E. American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol. 2004;22:3408–3419. - PubMed
    1. O'Connor ES, Greenblatt DY, LoConte NK, Gangnon RE, Liou JI, Heise CP, Smith MA. Adjuvant chemotherapy for stage II colon cancer with poor prognostic features. J Clin Oncol. 2011;29:3381–3388. - PMC - PubMed
    1. Galon J, Pages F, Marincola FM, Thurin M, Trinchieri G, Fox BA, Gajewski TF, Ascierto PA. The immune score as a new possible approach for the classification of cancer. J Transl Med. 2012;10(1) - PMC - PubMed