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Tumour-associated CD66b+ neutrophil count is an independent prognostic factor for recurrence in localised cervical cancer.

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.

SUBMITTER: Carus A

PROVIDER: S-EPMC3670536 | biostudies-other | 2013 May

REPOSITORIES: biostudies-other

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Project description:BackgroundEmerging evidence indicates that the tumor microenvironment influences tumor progression and patient prognosis through various inflammatory cells. Polymorphonuclear neutrophils (PMNs) and their functional structures termed neutrophil extracellular traps (NETs) are prominent constituents of several malignant tumors and affect the tumor microenvironment and cancer evolution. Here, we investigate the prognostic value of PMNs and NETs for recurrence in patients with cervical cancer.MethodsThe study comprised 126 cervical cancer patients who were retrospectively enrolled. CD66b+ neutrophils and myeloperoxidase/citrullinated histone H3 (MPO/H3Cit)-labeled NETs were assessed by immunofluorescence, and the relationships with clinical and histopathologic features and patient outcome were evaluated.ResultsThe highest density of CD66b+ neutrophils were observed in the stromal compartment (median 55 cells/mm2). Above median densities of stromal CD66b+ neutrophils and NETs were significantly associated with short recurrence-free survival (RFS) (P = 0.041 and P = 0.006, respectively). Multivariate analysis identified high clinical stage (hazard ratio [HR] 6.40; 95% confidence interval [CI] 3.51-11.64; P < 0.001), lymph node metastases (HR 4.69; 95% CI 3.09-9.66; P = 0.006) and high density of NETs (HR 2.66; 95% CI 1.21-5.82; P = 0.015) as independent prognostic factors for short RFS, whereas a high density of CD66b+ neutrophils was not significant. Patients with a high NET density showed worse recurrence status in every stage, but the difference was only significant for stage I (P = 0.042), not stages II, III, or IV (all P > 0.05). Combining stromal NET density and the tumor, nodes, metastasis (TNM) staging system had better prognostic accuracy for cervical cancer than the TNM staging system alone at five and six years respectively (P = 0.010 and P = 0.023).ConclusionStromal NET density is an independent prognostic factor for RFS in cervical cancer. Combining NETs with the TNM staging system may further improve prognostic stratification.

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Tumour-associated CD66b+ neutrophil count is an independent prognostic factor for recurrence in localised cervical cancer.

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