Tumour-infiltrating CD68+ and CD57+ cells predict patient outcome in stage II-III colorectal cancer

被引:37
作者
Chaput, N. [1 ]
Svrcek, M. [2 ]
Auperin, A. [3 ,4 ]
Locher, C. [1 ]
Drusch, F. [2 ]
Malka, D. [5 ]
Taieb, J. [6 ]
Goere, D. [7 ]
Ducreux, M. [5 ]
Boige, V. [5 ,8 ]
机构
[1] Inst Gustave Roussy, Ctr Clin Invest Biotherapy CIC BT 507, Villejuif, France
[2] Inst Gustave Roussy, Dept Pathol, Villejuif, France
[3] Inst Gustave Roussy, Dept Biostat, Villejuif, France
[4] Inst Gustave Roussy, Dept Epidemiol, Villejuif, France
[5] Inst Gustave Roussy, Dept Med Oncol, Villejuif, France
[6] Univ Paris 05, Hop Europeen Georges Pompidou, Serv Hepatogastroenterol & Oncol Digest, Paris, France
[7] Inst Gustave Roussy, Dept Surg, Villejuif, France
[8] INSERM, U981, Villejuif, France
关键词
colorectal cancer; prognosis; biomarker; tumour-infiltrating lymphocyte; tumour-infiltrating macrophage; CYTOTOXIC T-CELLS; MICROSATELLITE INSTABILITY; PROGNOSTIC-SIGNIFICANCE; INVASIVE MARGIN; IMMUNE-SYSTEM; EXPRESSION; LYMPHOCYTES; MICROENVIRONMENT; METASTASIS; SURVIVAL;
D O I
10.1038/bjc.2013.362
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Background: The aim of our study was to evaluate the prognostic role of immunological microenvironnement in stage II-III CRC patients. Methods: We constructed a tissue microarray from 196 consecutive patients with stage II-III CRC and compared CD3, CD4, CD8, CD57, CD68, CXCL9/MIG, CXCL13, and PPAR gamma immunoreactivity in tumour samples and their matched non-tumour tissue. We assessed their association with relapse-free survival (RFS; primary endpoint) and overall survival (OS) in multivariate Cox models. Results: Low densities of CD57+ and CD68+ tumour-infiltrating cells (TIC) independently predicted worse outcomes. A prognostic score combining CD57 (+, 4 vs -, <= 2 cells per spot) and CD68 (+, 40 vs -, -0 cells per spot) TIC density discriminated CRC patients at low (CD68+/CD57+), intermediate (CD68+/CD57-), or high (CD68-/CD57-) risk, with hazard ratios for the intermediate-risk and high-risk groups of 2.7 (95% confidence interval (CI): 1.3-5.8) and 9.0 (3.2-25.4) for RFS, and 2.5 (1.2-5.1) and 10.6 (3.8-29.2) for OS, respectively, as compared with the low-risk group. Corresponding 5-year survival rates (95% CI) in the low-, moderate-and high-risk groups were 84% (71-91), 65% (54-74), and 12% (2-47), respectively, for RFS, and 91% (80-96), 76% (66-84), and 25% (7-59), respectively, for OS. Conclusion: Tumour CD57+ and CD68+ TIC density assessment independently predicts survival in patients with stage II-III CRC. If validated, our score based on a quick, inexpensive, and well-established method such as point counting on diagnostic tissue sections could be used routinely as a prognostic tool in CRC patients.
引用
收藏
页码:1013 / 1022
页数:10
相关论文
共 49 条
[1]
ColoGuideEx: a robust gene classifier specific for stage II colorectal cancer prognosis [J].
Agesen, Trude H. ;
Sveen, Anita ;
Merok, Marianne A. ;
Lind, Guro E. ;
Nesbakken, Arild ;
Skotheim, Rolf I. ;
Lothe, Ragnhild A. .
GUT, 2012, 61 (11) :1560-1567
[2]
AJCC, 2010, AM JOINT COMMITTEE C
[3]
Type and location of tumor-infiltrating macrophages and lymphatic vessels predict survival of colorectal cancer patients [J].
Algars, Annika ;
Irjala, Heikki ;
Vaittinen, Samuli ;
Huhtinen, Heikki ;
Sundstrom, Jari ;
Salmi, Marko ;
Ristamaki, Raija ;
Jalkanen, Sirpa .
INTERNATIONAL JOURNAL OF CANCER, 2012, 131 (04) :864-873
[4]
Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer [J].
Andre, T ;
Boni, C ;
Mounedji-Boudiaf, L ;
Navarro, M ;
Tabernero, J ;
Hickish, T ;
Topham, C ;
Zaninelli, M ;
Clingan, P ;
Bridgewater, J ;
Tabah-Fisch, I ;
de Gramont, A .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 350 (23) :2343-2351
[5]
Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy [J].
Apetoh, Lionel ;
Ghiringhelli, Francois ;
Tesniere, Antoine ;
Obeid, Michel ;
Ortiz, Carla ;
Criollo, Alfredo ;
Mignot, Gregoire ;
Maiuri, M. Chiara ;
Ullrich, Evelyn ;
Saulnier, Patrick ;
Yang, Huan ;
Amigorena, Sebastian ;
Ryffel, Bernard ;
Barrat, Franck J. ;
Saftig, Paul ;
Levi, Francis ;
Lidereau, Rosette ;
Nogues, Catherine ;
Mira, Jean-Paul ;
Chompret, Agnes ;
Joulin, Virginie ;
Clavel-Chapelon, Francoise ;
Bourhis, Jean ;
Andre, Fabrice ;
Delaloge, Suzette ;
Tursz, Thomas ;
Kroemer, Guido ;
Zitvogel, Laurence .
NATURE MEDICINE, 2007, 13 (09) :1050-1059
[6]
LYMPHOKINE-ACTIVATED KILLER-CELL FUNCTION OF LYMPHOCYTES FROM REGIONAL LYMPH-NODES IN PATIENTS WITH GASTRIC-CARCINOMA [J].
ARINAGA, S ;
KARIMINE, N ;
NANBARA, S ;
INOUE, H ;
NAKASHIMA, H ;
UEO, H ;
AKIYOSHI, T .
JOURNAL OF SURGICAL ONCOLOGY, 1995, 58 (01) :44-49
[7]
Prognostic value of indoleamine 2,3-dioxygenase expression in colorectal cancer:: Effect on tumor-infiltrating T cells [J].
Brandacher, G ;
Perathoner, A ;
Ladurner, R ;
Schneeberger, S ;
Obrist, P ;
Winkler, C ;
Werner, ER ;
Werner-Felmayer, G ;
Weiss, HG ;
Göbel, G ;
Margreiter, R ;
Königsrainer, A ;
Fuchs, D ;
Amberger, A .
CLINICAL CANCER RESEARCH, 2006, 12 (04) :1144-1151
[8]
Coca S, 1997, CANCER-AM CANCER SOC, V79, P2320, DOI 10.1002/(SICI)1097-0142(19970615)79:12<2320::AID-CNCR5>3.0.CO
[9]
2-P
[10]
Prognostic value of the CD4+/CD8+ ratio of tumour infiltrating lymphocytes in colorectal cancer and HLA-DR expression on tumour cells [J].
Diederichsen, ACP ;
Hjelmborg, JV ;
Christensen, PB ;
Zeuthen, J ;
Fenger, C .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2003, 52 (07) :423-428