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Tumour-associated CD66b+ neutrophil count is an independent prognostic factor for recurrence in localised cervical cancer
Authors:A Carus  M Ladekarl  H Hager  B S Nedergaard  F Donskov
Institution:1.Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark;2.Department of Oncology, Aarhus University Hospital, Aarhus, Denmark;3.Department of Pathology, Aarhus University Hospital,, Aarhus, Denmark;4.Department of Pathology, Aalborg Hospital, and Stereology and Electron Microscopy Research Laboratory, Aarhus University Hospital, Aarhus, Denmark
Abstract:

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.
Keywords:tumour-associated neutrophils  tumour-associated macrophages  stereology  cancer inflammation  cervix carcinoma
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