Journal
BRITISH JOURNAL OF CANCER
Volume 108, Issue 10, Pages 2116-2122Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2013.167
Keywords
tumour-associated neutrophils; tumour-associated macrophages; stereology; cancer inflammation; cervix carcinoma
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Funding
- Danish Cancer Society
- Beckett Foundation
- Danish Cancer Research Foundation
- Max and Inger Woerzner Foundation
- A.P. Moller and Chastine Mc-Kinney Moller's Foundation
- Jacob Madsens and Olga Madsens Foundation
- Harboe Foundation
- foundation of the family Kjaersgaards, Sunds
- Institute of Clinical Medicine
- Radiumstationens Forskningsfond
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Background: The prognostic impact of tumour-promoting immune cells in cervical cancer is unclear. Methods: Federation of Gynaecology and Obstetrics (FIGO) stage IB and IIA cervical cancer patients (N = 101) were assessed for tumour-associated CD66b(+) neutrophils and CD163(+) macrophages by immunohistochemistry in whole tissue sections using stereology. Results were correlated with previous results on tumour-infiltrating CD3(+), CD4(+), and CD8(+) lymphocytes in the same cohort with recurrence-free survival (RFS) as end point. Results: The highest densities of CD66b(+) neutrophils and CD163(+) macrophages were observed in the peritumoural compartment (median 53.1 cells mm(-2) and 1.3% area fraction, respectively). Above median peritumoural and stromal CD66b(+) neutrophils and peritumoural CD163(+) macrophages were significantly associated with short RFS. Multivariate analysis identified high peritumoural neutrophils (HR 2.27; 95% CI 1.09-4.75; P = 0.03), low peritumoural CD8(+) lymphocytes (HR 3.67; 95% CI 1.63-8.25; P = 0.002), and lymph node metastases (HR 2.70; 95% CI 1.26-5.76; P = 0.01) as independent prognostic factors for short RFS, whereas CD163(+) macrophages were not significant. An index of combined intratumoral and peritumoral CD66b(+) neutrophils to CD8(+) lymphocytes had good discriminatory power for each quartile with 5-year RFS of 92%, 80%, 62%, and 44% (P = 0.001). Conclusion: Tumour-associated neutrophil count is an independent prognostic factor for short RFS in localised cervical cancer. Combining CD66b and CD8 may further improve prognostic stratification. These findings require prospective validation.
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