Neutrophil infiltration combined with necrosis in the primary tumor is a useful prognostic indicator for three‑year disease‑free survival time in patients with colorectal cancer

Abstract

Histopathological evaluation plays a key role in the diagnosis of colorectal cancer (CRC). Tumor-related local inflammation is regarded as a novel prognostic parameter. Neutrophils constitute one of the main types of inflammatory cells. The aim of the present study was to evaluate the prognostic value of intratumoral tumor-associated neutrophils (intraTANs), stromal TANs (stromaTANs) and necrosis, as well as their combined parametric value in formalin-fixed paraffin-embedded tissue sections from patients with CRC. For this purpose, a retrospective study of 160 patients with CRC who underwent surgery was conducted. The association of intraTANs, stromaTANs, necrosis and their combined parametric value with the clinicopathological features of patients with CRC was examined. The Kaplan-Meier method and the log-rank test were used to compare survival curves. To identify independent prognostic factors, uni-and multivariate Cox proportional hazards regression models were used. StromaTANs were associated with lymph node metastasis (P=0.049) and tumor deposits (P=0.041). In addition, necrosis was found to be associated with venous (P=0.003), lymphatic (P=0.007) and perineural (P=0.015) invasion, as well as with lymph node metastasis (P=0.033), the number of invaded lymph nodes (P=0.012), and lymph node pouch invasion (P=0.043). Furthermore, necrosis was found to be associated with the white blood cell count (P=0.030), neutrophil count (P=0.011), the combined neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (NLR-PLR) (P=0.038), and the combined platelet and NLR (PLT-NLR status) (P=0.030), as well as with the serum carcinoembryonic antigen (CEA) levels following surgery (P=0.011) and the monocyte-to-lymphocyte ratio (P=0.023). The combined parametric value was found to be associated with pT stage (P=0.049), venous (P=0.034) and lymphatic (P=0.026) invasion, and with serum CEA levels prior to surgery (P=0.029). The analysis of the 3-year disease-free survival (DFS) time revealed that tumor growth [hazard ratio (HR), 2.070; 95% CI, 1.837-3.808; P= 0.003] and the combined parametric value (intraTANs, stromaTANs and necrosis, HR, 1.577; 95% CI, 1.372-3.032; P= 0.028) were independent factors for patients with CRC. Taken together, the findings of the present study demonstrated that the combined value of neutrophils and necrosis examined in the cancerous tissue may be used as a prognostic factor for the 3-year DFS time in patients with CRC.

Immunological variables and tumor types influence one-year survival probability in cancer patients: A comprehensive analysis using logistic regression and decision tree models

“…Contrary to this hypothesis, the presence of necrotic tissue in the sample did not correlate with survival (Days to death), but it did correlate slightly with the percentage of neutrophils (cor=0.3). Detection of neutrophils in necrotic tissues is a favorable prognostic indicator for some types of tumors 8 .…”

Neutrophil–lymphocyte ratio reflects tumour‐infiltrating lymphocytes and tumour‐associated macrophages and independently predicts poor outcome in breast cancers with neoadjuvant chemotherapy

“…34 It has been suggested that cancer-associated inflammatory cytokinesfor example, tumour necrosis factor alpha and colonystimulating factorcontribute to the increase of neutrophil count, 1,35 or that a high neutrophil count signifies or favours response by tumour necrosis. 36 High NLR reflects increased inflammatory activity attributable to cancer burden, proliferation and/or progression which, in turn, is prognostically significant. 1,2 This postulation agrees with the finding that a late increase in NLR is associated with poor outcomes.…”

“…The positive association between NLR, tumour necrosis and TAMs has been reported in hepatopancreatic tumours, 32,33 but for breast cancers a literature search only yielded a smaller cohort, which failed to demonstrate associations between NLR and tumour necrosis in breast cancer 34 . It has been suggested that cancer‐associated inflammatory cytokines – for example, tumour necrosis factor alpha and colony‐stimulating factor – contribute to the increase of neutrophil count, 1,35 or that a high neutrophil count signifies or favours response by tumour necrosis 36 . High NLR reflects increased inflammatory activity attributable to cancer burden, proliferation and/or progression which, in turn, is prognostically significant 1,2 .…”

Necrosis score as a prognostic factor in stage I–III colorectal cancer: a retrospective multicenter study

“…Necrosis has been receiving much attention in the prognosis prediction of CRC [ 14 , 20 , 21 ]. Increased hypoxia due to abnormal rates of cell division, development of solid tumor masses that disrupt vascular penetration, resulting in decreased oxygen diffusion [ 22 ].…”