The prognostic value of tumor-infiltrating neutrophils in gastric adenocarcinoma after resection.

State Key Laboratory of Oncology in Southern China and Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.
PLoS ONE (Impact Factor: 3.53). 01/2012; 7(3):e33655. DOI: 10.1371/journal.pone.0033655
Source: PubMed

ABSTRACT Several pieces of evidence indicate that tumor-infiltrating neutrophils (TINs) are correlated to tumor progression. In the current study, we explore the relationship between TINs and clinicopathological features of gastric adenocarcinoma patients. Furthermore, we investigated the prognostic value of TINs.
The study was comprised of two groups, training group (115 patients) and test group (97 patients). Biomarkers (intratumoral CD15+ neutrophils) were assessed by immunohistochemistry. The relationship between clinicopathological features and patient outcome were evaluated using Cox regression and Kaplan-Meier analysis.
Immunohistochemical detection showed that the tumor-infiltrating neutrophils (TINs) in the training group ranged from 0.00-115.70 cells/high-power microscopic field (HPF) and the median number was 21.60 cells/HPF. Based on the median number, the patients were divided into high and low TINs groups. Chi-square test analysis revealed that the density of CD15+ TINs was positively associated with lymph node metastasis (p = 0.024), distance metastasis (p = 0.004) and UICC (International Union Against Cancer) staging (p = 0.028). Kaplan-Meier analysis showed that patients with a lower density of TINs had a better prognosis than patients with a higher density of TINs (p = 0.002). Multivariate Cox's analysis showed that the density of CD15+ TINs was an independent prognostic factor for overall survival of gastric adenocarcinoma patients. Using another 97 patients as a test group and basing on the median number of TINs (21.60 cells/HPF) coming from the training group, Kaplan-Meier analysis also showed that patients with a lower density of TINs had a better prognosis than patients with a higher density of TINs (p = 0.032). The results verify that the number of CD15+ TINs can predict the survival of gastric adenocarcinoma surgical patients.
The presence of CD15+ TINs is an independent and unfavorable factor in the prognosis of gastric adenocarcinoma patients. Targeting CD15+ TINs may be a potential intervenient therapy in the future.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The interaction between tumor cells and inflammatory cells has not been systematically investigated in esophageal squamous cell carcinoma (ESCC). The main aims of the study were to investigate the clinical significance of tumor-infiltrating neutrophils and neturophil-to-CD8+ lymphocyte ratio (NLR), and to analyze the distribution of tumor-infiltrating neutrophils and CD8+ lymphocytes in ESCC treated by curative resection. The expressions of CD66b and CD8 were assessed with double staining immunohistochemistry in the surgical specimens from 90 patients with ESCC treated by curative surgery. We showed that increased intratumoral neutrophils were significantly associated with lymph node metastasis (P = 0.016), and advanced pathological stages (P = 0.013). Decreased peritumoral CD8+ lymphocyte density was more frequently observed in patients with single positive lymph node (p = 0.045). Peritumoral NLR was significantly associated with advanced T stages (p < 0.001), lymph node metastasis (p = 0.041) and a trend towards advanced pathological stages (p = 0.053). Increased intratumoral neutrophils were significantly associated with decreased disease-free survival (p < 0.001) and overall survival (p < 0.001) in univariate analysis and were identified as an independent prognostic factor for disease-free survival (p = 0.006) and overall survival (p = 0.037) in multivariate analysis. Neither the density nor the distribution of tumor-infiltrating neutrophils was significantly correlated with that of CD8+ lymphocytes. The density of intratumoral CD8+ lymphocytes was significantly lower than (P < 0.001) and moderately correlated with (r = 0.434, p < 0.001) that in peritumoral area. Increased intratumoral neutrophils were an independent poor prognostic factor and peritumoral NLR was significantly associated with disease progression in ESCC treated by curative surgery, suggesting the possible effect of immune misbalance of tumor microenvironment in facilitating ESCC progression. Immunotherapy targeted to the above predictors should be considered in the future.
    Journal of Translational Medicine 01/2014; 12(1):7. · 3.46 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Gastric cancer (GC), which is mainly induced by Helicobacter pylori (H. pylori) infection, is one of the leading causes of cancer-related death in the developing world. Active inflammation initiated by H. pylori infection and maintained by inherent immune disorders promotes carcinogenesis and postoperative recurrence. However, the presence with H. pylori in tumors has been linked to a better prognosis, possibly due to the induction of antitumor immunity. Tumor infiltrations of tumor-associated macrophages, myeloid-derived suppressor cells, neutrophils, Foxp3(+) regulatory T cells are correlated with poor prognosis. Tumor infiltrating CD8(+) cytotoxic T lymphocytes, dendritic cells, and CD45RO T cells are generally associated with good prognosis of GC, although some subsets of these immune cells have inverse prognosis prediction values. High ratios of Foxp3(+)/CD4(+) and Foxp3(+)/CD8(+) in tumors are associated with a poor prognosis; whereas high Th1/Th2 ratio in tumors predicts a good prognosis. High levels of interleukin (IL)-6, IL-10, IL-32, and chemokine C-C motif ligands (CCL)7 and CCL21 in circulation, high expression of CXC chemokine receptor 4, chemokine C-C motif receptor (CCR)3, CCR4, CCR5, CCR7, hypoxia-inducible factor-1α, signal transducer activator of transcription-3, cyclooxygenase-2, and orphan nuclear receptor 4A2 in tumors are associated with an unfavorable prognosis. Increased serum levels of matrix metalloproteinases (MMP)-3, MMP-7, and MMP-11 and increased levels of MMP-9, MMP-12, and MMP-21 in tumors are consistently associated with poor survival of GC. Further emphasis should be put on the integration of these biomarkers and validation in large cohorts for personalized prediction of GC postoperative prognosis.
    World Journal of Gastroenterology 04/2014; 20(16):4586-4596. · 2.55 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background and Objectives Elevated preoperative neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) predict survival rates among patients with several types of cancer. The current study sought to clarify whether NLR and PLR are clinically useful independent prognostic indicators of adenocarcinomas of the esophagogastric junction (AEG) among patients undergoing curative resections (i.e., R0 resections).MethodsA total of 327 patients who underwent R0 resections for AEG were enrolled in the study. Data concerning demographic parameters, laboratory analyses, histopathology, and survival time were collected and analyzed.ResultsA total of 123 patients (37.6%) had elevated preoperative NLR (≥5). The median follow-up duration was 24.7 months (range = 2–39 months). NLR was significantly related to histology (P = 0.035), pTNM stage (P < 0.0001) and tumor recurrence (P = 0.022). Univariate analyses revealed that NLR were significantly associated with disease-free survival (DFS) and overall survival (OS; both P < 0.0001). Multivariable analyses revealed that elevated NLR independently predicted poorer DFS (hazard ratio [HR] = 2.551, P < 0.0001) and OS (HR = 2.743, P < 0.0001). However, PLR did not significantly predict DFS or OS.Conclusion The present study indicates that elevated preoperative NLR (≥5) is a useful marker of tumor recurrence and independently predicts poorer disease-free and overall survival among patients with AEG undergoing R0 resections. J. Surg. Oncol. © 2014 Wiley Periodicals, Inc.
    Journal of Surgical Oncology 05/2014; · 2.64 Impact Factor

Full-text (3 Sources)

Available from
Jun 3, 2014