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.

Figure 1

(A) Representative example of CD66b⁺/CD34⁺ staining (20x lens) with tumour nest neutrophil (black thin arrow) and peritumoural neutrophil (white thin arrow). An unbiased counting frame is applied. (B) CD163⁺ immunostaining (20x lens) illustrating tumour nest macrophage (black fat arrow) and peritumoural macrophages (white fat arrow). A counting grid is applied.

Figure 2

Kaplan–Meier RFS curves according to peritumoural CD66b⁺ neutrophils (A), peritumoural CD163⁺ macrophages (B), and peritumoral CD8⁺ lymphocytes (C), all stratified by medians, and according to presence or absence of lymph node metastases (D). P-values obtained from log-rank tests.

Figure 3

Kaplan–Meier recurrence-free survival curves according to the TA-NLR stratified at quartiles from lower quartile I to highest quartile IV. P-value obtained from log-rank test.