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Published in: BMC Cancer 1/2019

Open Access 01-12-2019 | Colon Cancer | Research article

Programmed Death Ligand-1 expression in stage II colon cancer - experiences from a nationwide populationbased cohort

Authors: Ann C. Eriksen, Flemming B. Sørensen, Jan Lindebjerg, Henrik Hager, René dePont Christensen, Sanne Kjær-Frifeldt, Torben F. Hansen

Published in: BMC Cancer | Issue 1/2019

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Abstract

Background

Patients suffering from high risk stage II colon cancer (CC) may benefit from adjuvant onco-therapy, but additional prognostic markers are needed for better treatment stratification. We investigated the prognostic value of Programmed Death Ligand-1 (PD-L1) in a true population-based cohort of patients with stage II CC.

Methods

PD-L1 expression on tumour cells was evaluated by immunohistochemistry in 572 colon cancers. Whole sections from tumour blocks representing the deepest invasive front of the primary tumour were used for analysis. A cut-off of 5% positivity was used for dichotomizing the data. The prognostic value was investigated in Cox proportional hazard models for recurrence-free survival (RFS) and overall survival (OS).

Results

Overall, 6% of the tumours were classified as high PD-L1. High PD-L1 was related to female gender (p = 0.028), high malignancy grade (< 0.001), right side localization (p < 0.001) and microsatellite instability (MSI) (p < 0.001). Thirty-one (18%) of the MSI and 4 (1%) of the microsatellite stable tumours were classified as high PD-L1, respectively. PD-L1 expression provided no prognostic value as a single marker. In patients with MSI tumours, high PD-L1 expression had no significant impact regarding OS or RFS.

Conclusions

PD-L1 expression in tumour cells of stage II CC did not provide any prognostic impact, neither in the entire population-based cohort nor in the group of MSI patients. Additional investigations of the immunogenic microenvironment are needed for evaluating the prognostic information in CC.
Literature
1.
go back to reference Morris M, Platell C, McCaul K, Millward M, van Hazel G, Bayliss E, et al. Survival rates for stage II colon cancer patients treated with or without chemotherapy in a population-based setting. Int J Color Dis. 2007;22(8):887–95.CrossRef Morris M, Platell C, McCaul K, Millward M, van Hazel G, Bayliss E, et al. Survival rates for stage II colon cancer patients treated with or without chemotherapy in a population-based setting. Int J Color Dis. 2007;22(8):887–95.CrossRef
2.
go back to reference Labianca R, Nordlinger B, Beretta GD, Mosconi S, Mandala M, Cervantes A, et al. Early colon cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24(6):64–72. Labianca R, Nordlinger B, Beretta GD, Mosconi S, Mandala M, Cervantes A, et al. Early colon cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24(6):64–72.
3.
go back to reference Benson AB 3rd, Schrag D, Somerfield MR, Cohen AM, Figueredo AT, Flynn PJ, et al. American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol. 2004;22(16):3408–19.PubMedCrossRef Benson AB 3rd, Schrag D, Somerfield MR, Cohen AM, Figueredo AT, Flynn PJ, et al. American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol. 2004;22(16):3408–19.PubMedCrossRef
4.
go back to reference O'Connor ES, Greenblatt DY, LoConte NK, Gangnon RE, Liou JI, Heise CP, et al. Adjuvant chemotherapy for stage II colon cancer with poor prognostic features. J Clin Oncol. 2011;29(25):3381–8.PubMedPubMedCentralCrossRef O'Connor ES, Greenblatt DY, LoConte NK, Gangnon RE, Liou JI, Heise CP, et al. Adjuvant chemotherapy for stage II colon cancer with poor prognostic features. J Clin Oncol. 2011;29(25):3381–8.PubMedPubMedCentralCrossRef
5.
go back to reference Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39(1):1–10.PubMedCrossRef Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39(1):1–10.PubMedCrossRef
6.
go back to reference Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;313(5795):1960–4.PubMedCrossRef Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;313(5795):1960–4.PubMedCrossRef
7.
go back to reference Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002;8(8):793–800.PubMedCrossRef Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002;8(8):793–800.PubMedCrossRef
8.
go back to reference Keir ME, Francisco LM, Sharpe AH. PD-1 and its ligands in T-cell immunity. Curr Opin Immunol. 2007;19(3):309–14.PubMedCrossRef Keir ME, Francisco LM, Sharpe AH. PD-1 and its ligands in T-cell immunity. Curr Opin Immunol. 2007;19(3):309–14.PubMedCrossRef
9.
go back to reference Kim JH, Park HE, Cho NY, Lee HS, Kang GH. Characterisation of PD-L1-positive subsets of microsatellite-unstable colorectal cancers. Br J Cancer. 2016;115(4):490–6.PubMedPubMedCentralCrossRef Kim JH, Park HE, Cho NY, Lee HS, Kang GH. Characterisation of PD-L1-positive subsets of microsatellite-unstable colorectal cancers. Br J Cancer. 2016;115(4):490–6.PubMedPubMedCentralCrossRef
10.
go back to reference Rosenbaum MW, Bledsoe JR, Morales-Oyarvide V, Huynh TG, Mino-Kenudson M. PD-L1 expression in colorectal cancer is associated with microsatellite instability, BRAF mutation, medullary morphology and cytotoxic tumor-infiltrating lymphocytes. Mod Pathol. 2016;29(9):1104–12.PubMedCrossRef Rosenbaum MW, Bledsoe JR, Morales-Oyarvide V, Huynh TG, Mino-Kenudson M. PD-L1 expression in colorectal cancer is associated with microsatellite instability, BRAF mutation, medullary morphology and cytotoxic tumor-infiltrating lymphocytes. Mod Pathol. 2016;29(9):1104–12.PubMedCrossRef
11.
go back to reference Lee LH, Cavalcanti MS, Segal NH, Hechtman JF, Weiser MR, Smith JJ, et al. Patterns and prognostic relevance of PD-1 and PD-L1 expression in colorectal carcinoma. Mod Pathol. 2016;29(11):1433–42.PubMedPubMedCentralCrossRef Lee LH, Cavalcanti MS, Segal NH, Hechtman JF, Weiser MR, Smith JJ, et al. Patterns and prognostic relevance of PD-1 and PD-L1 expression in colorectal carcinoma. Mod Pathol. 2016;29(11):1433–42.PubMedPubMedCentralCrossRef
12.
go back to reference Koganemaru S, Inoshita N, Miura Y, Miyama Y, Fukui Y, Ozaki Y, et al. Prognostic value of programmed death-ligand 1 expression in patients with stage III colorectal cancer. Cancer Sci. 2017;108(5):853–8.PubMedPubMedCentralCrossRef Koganemaru S, Inoshita N, Miura Y, Miyama Y, Fukui Y, Ozaki Y, et al. Prognostic value of programmed death-ligand 1 expression in patients with stage III colorectal cancer. Cancer Sci. 2017;108(5):853–8.PubMedPubMedCentralCrossRef
13.
go back to reference Masugi Y, Nishihara R, Yang J, Mima K, da Silva A, Shi Y, et al. Tumour CD274 (PD-L1) expression and T cells in colorectal cancer. Gut. 2017;66(8):1463–73.PubMedCrossRef Masugi Y, Nishihara R, Yang J, Mima K, da Silva A, Shi Y, et al. Tumour CD274 (PD-L1) expression and T cells in colorectal cancer. Gut. 2017;66(8):1463–73.PubMedCrossRef
14.
go back to reference Lee KS, Kwak Y, Ahn S, Shin E, Oh HK, Kim DW, et al. Prognostic implication of CD274 (PD-L1) protein expression in tumor-infiltrating immune cells for microsatellite unstable and stable colorectal cancer. Cancer immunology. Immunotheraphy. 2017;66(7):927–39.CrossRef Lee KS, Kwak Y, Ahn S, Shin E, Oh HK, Kim DW, et al. Prognostic implication of CD274 (PD-L1) protein expression in tumor-infiltrating immune cells for microsatellite unstable and stable colorectal cancer. Cancer immunology. Immunotheraphy. 2017;66(7):927–39.CrossRef
15.
go back to reference Li Y, Liang L, Dai W, Cai G, Xu Y, Li X, et al. Prognostic impact of programed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) expression in cancer cells and tumor infiltrating lymphocytes in colorectal cancer. Mol Cancer. 2016;15(1):55.PubMedPubMedCentralCrossRef Li Y, Liang L, Dai W, Cai G, Xu Y, Li X, et al. Prognostic impact of programed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) expression in cancer cells and tumor infiltrating lymphocytes in colorectal cancer. Mol Cancer. 2016;15(1):55.PubMedPubMedCentralCrossRef
16.
go back to reference McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM. REporting recommendations for tumour MARKer prognostic studies (REMARK). Br J Cancer. 2005;93(4):387–91.PubMedPubMedCentralCrossRef McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM. REporting recommendations for tumour MARKer prognostic studies (REMARK). Br J Cancer. 2005;93(4):387–91.PubMedPubMedCentralCrossRef
17.
go back to reference Eriksen AC, Sørensen FB, Lindebjerg J, Hager H, dePont Christensen R, Kjær-Frifeldt S, et al. The prognostic value of tumour infiltrating lymphocytes in stage II colon cancer. A nationwide population-based study. Transl Oncol. 2018;11(4):979–87.PubMedPubMedCentralCrossRef Eriksen AC, Sørensen FB, Lindebjerg J, Hager H, dePont Christensen R, Kjær-Frifeldt S, et al. The prognostic value of tumour infiltrating lymphocytes in stage II colon cancer. A nationwide population-based study. Transl Oncol. 2018;11(4):979–87.PubMedPubMedCentralCrossRef
18.
go back to reference Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977;33(1):159–74.CrossRef Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977;33(1):159–74.CrossRef
19.
go back to reference Korehisa S, Oki E, Iimori M, Nakaji Y, Shimokawa M, Saeki H, et al. Clinical significance of programmed cell death-ligand 1 expression and the immune microenvironment at the invasive front of colorectal cancers with high microsatellite instability. Int J Cancer. 2018;142(4):822–32.PubMedCrossRef Korehisa S, Oki E, Iimori M, Nakaji Y, Shimokawa M, Saeki H, et al. Clinical significance of programmed cell death-ligand 1 expression and the immune microenvironment at the invasive front of colorectal cancers with high microsatellite instability. Int J Cancer. 2018;142(4):822–32.PubMedCrossRef
20.
go back to reference Zhang Y, Sun Z, Mao X, Wu H, Luo F, Wu X, et al. Impact of mismatch-repair deficiency on the colorectal cancer immune microenvironment. Oncotarget. 2017;8(49):85526–36.PubMedPubMedCentral Zhang Y, Sun Z, Mao X, Wu H, Luo F, Wu X, et al. Impact of mismatch-repair deficiency on the colorectal cancer immune microenvironment. Oncotarget. 2017;8(49):85526–36.PubMedPubMedCentral
21.
go back to reference Boissiere-Michot F, Lazennec G, Frugier H, Jarlier M, Roca L, Duffour J, et al. Characterization of an adaptive immune response in microsatellite-instable colorectal cancer. Oncoimmunology. 2014;3:e29256.PubMedPubMedCentralCrossRef Boissiere-Michot F, Lazennec G, Frugier H, Jarlier M, Roca L, Duffour J, et al. Characterization of an adaptive immune response in microsatellite-instable colorectal cancer. Oncoimmunology. 2014;3:e29256.PubMedPubMedCentralCrossRef
22.
23.
go back to reference Guinney J, Dienstmann R, Wang X, de Reynies A, Schlicker A, Soneson C, et al. The consensus molecular subtypes of colorectal cancer. Nat Med. 2015;21(11):1350–6.PubMedPubMedCentralCrossRef Guinney J, Dienstmann R, Wang X, de Reynies A, Schlicker A, Soneson C, et al. The consensus molecular subtypes of colorectal cancer. Nat Med. 2015;21(11):1350–6.PubMedPubMedCentralCrossRef
24.
go back to reference Reilley M, Blando JM, Katkhuda R, Menter D, Sharma P, Allison JP, et al. Immunologic profiling of consensus molecular subtype (CMS) stratified colorectal cancer (CRC) primary and liver metastectomy specimens: implications for immune targeting of proficient mismatch repair CRC. J Clin Oncol. 2016;34(15):3520.CrossRef Reilley M, Blando JM, Katkhuda R, Menter D, Sharma P, Allison JP, et al. Immunologic profiling of consensus molecular subtype (CMS) stratified colorectal cancer (CRC) primary and liver metastectomy specimens: implications for immune targeting of proficient mismatch repair CRC. J Clin Oncol. 2016;34(15):3520.CrossRef
25.
go back to reference Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372(21):2018–28.PubMedCrossRef Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372(21):2018–28.PubMedCrossRef
26.
go back to reference Zlobec I, Terracciano L, Jass JR, Lugli A. Value of staining intensity in the interpretation of immunohistochemistry for tumor markers in colorectal cancer. Virchows Arch. 2007;451(4):763–9.PubMedCrossRef Zlobec I, Terracciano L, Jass JR, Lugli A. Value of staining intensity in the interpretation of immunohistochemistry for tumor markers in colorectal cancer. Virchows Arch. 2007;451(4):763–9.PubMedCrossRef
27.
go back to reference Sunshine JC, Nguyen PL, Kaunitz GJ, Cottrell TR, Berry S, Esandrio J, et al. PD-L1 expression in melanoma: a quantitative Immunohistochemical antibody comparison. Clin Cancer Res. 2017;23(16):4938–44.PubMedPubMedCentralCrossRef Sunshine JC, Nguyen PL, Kaunitz GJ, Cottrell TR, Berry S, Esandrio J, et al. PD-L1 expression in melanoma: a quantitative Immunohistochemical antibody comparison. Clin Cancer Res. 2017;23(16):4938–44.PubMedPubMedCentralCrossRef
Metadata
Title
Programmed Death Ligand-1 expression in stage II colon cancer - experiences from a nationwide populationbased cohort
Authors
Ann C. Eriksen
Flemming B. Sørensen
Jan Lindebjerg
Henrik Hager
René dePont Christensen
Sanne Kjær-Frifeldt
Torben F. Hansen
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2019
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-019-5345-6

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