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. 2012;7(1):e30806.
doi: 10.1371/journal.pone.0030806. Epub 2012 Jan 25.

Increased intratumoral neutrophil in colorectal carcinomas correlates closely with malignant phenotype and predicts patients' adverse prognosis

Hui-Lan Rao  1 , Jie-Wei Chen, Mei Li, Yong-Bo Xiao, Jia Fu, Yi-Xin Zeng, Mu-Yan Cai, Dan Xie
Affiliations

Increased intratumoral neutrophil in colorectal carcinomas correlates closely with malignant phenotype and predicts patients' adverse prognosis

Hui-Lan Rao et al. PLoS One. 2012.

Abstract

Background: Substantial evidence suggests that the presence of inflammatory cells plays a critical role in the development and/or progression of human tumors. Neutrophils are the common inflammatory cells in tumors; however, the infiltration of intratumoral neutrophils in colorectal carcinoma (CRC) and its effect on CRC patients' prognosis are poorly understood.

Methodology/principal findings: In this study, the methods of tissue microarray and immunohistochemistry (IHC) were used to investigate the prognostic significance of intratumoral CD66b+ neutrophil in CRC. According to receiver operating characteristic curve analysis, the cutoff score for high intratumoral CD66b+ neutrophil in CRC was defined when the mean counts were more than 60 per TMA spot. In our study, high intratumoral CD66b+ neutrophil was observed in 104/229 (45.4%) of CRCs and in 29/229 (12.7%) of adjacent mucosal tissues. Further correlation analysis showed that high intratumoral neutrophil was positively correlated with pT status, pM status and clinical stage (P<0.05). In univariate survival analysis, a significant association between high intratumoral neutrophil and shortened patients' survival was found (P<0.0001). In different subsets of CRC patients, intratumoral neutrophil was also a prognostic indicator in patients with stage II, stage III, grade 2, grade 3, pT1, pT2, pN0 and pN1 (P<0.05). Importantly, high intratumoral neutrophil was evaluated as an independent prognostic factor in multivariate analysis (P<0.05).

Conclusions/significance: Our results provide evidence that increased intratumoral neutrophil in CRC may be important in the acquisition of a malignant phenotype, indicating that the presence of intratumoral neutrophil is an independent factor for poor prognosis of patients with CRC.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. ROC curve analysis was employed to determine the cutoff value for high intratumoral CD66b+ neutrophil in colorectal carcinoma.
The sensitivity and specificity for each outcome were plotted: tumor grade (P = 0.575, A), T stage (P = 0.029, B), N stage (P = 0.263, C), M stage (P = 0.002, D), clinical stage (P = 0.005, E), and survival status (P<0.001, F).
Figure 2
Figure 2. The presence of CD66b+ neutrophils in colorectal and lymph node metastatic CRC tissues.
(A) High intratumoral neutrophil was observed in a CRC (case 52), in which more than 60 intratumoral cells revealed positive immunostaining of CD66b (upper panel, ×100). (B) A CRC case (case 37) demonstrated low intratumoral neutrophil, in which less than 60 intratumoral cells showed immunoreactivity of CD66b (upper panel, ×100). (C) The corresponding adjacent mucosal tissue of case 52 showed low neutrophil, in which less than 60 cells revealed immunostaining of CD66b (upper panel, ×100). (D) High intratumoral neutrophil was observed in lymph node metastatic tissue, in which more than 60 intratumoral cells revealed positive immunostaining of CD66b (upper panel, ×100). The lower panels indicated the higher magnification (×400) from the area of the box in A, B and C, respectively.
Figure 3
Figure 3. Survival curves for 229 CRC patients according to infiltration status of intratumoral neutrophils (log-rank test).
(A) Total, probability of survival of all patients with CRC: low intratumoral neutrophil, n = 125; high intratumoral neutrophil, n = 104. (B) Stage II, probability of survival of stage II patients with CRC: low intratumoral neutrophil, n = 44; high intratumoral neutrophil, n = 32. (C) Stage III, probability of survival of stage III patients with CRC: low intratumoral neutrophil, n = 27; high intratumoral neutrophil, n = 29. (D) Stage IV, probability of survival of stage IV patients with CRC: low intratumoral neutrophil, n = 5; high intratumoral neutrophil, n = 18.
Figure 4
Figure 4. Survival curves according to infiltration status of intratumoral neutrophils in subsets of CRC patients with different histological grade and pT/pN status (log-rank test).
(A) Grade 2, probability of survival of grade 2 patients with CRC: low intratumoral neutrophil, n = 93; high intratumoral neutrophil, n = 81. (B) Grade 3, probability of survival of grade 3 patients with CRC: low intratumoral neutrophil, n = 20; high intratumoral neutrophil, n = 16. (C) pT2, probability of survival of pT2 patients with CRC: low intratumoral neutrophil, n = 45; high intratumoral neutrophil, n = 31. (D) pT3, probability of survival of pT2 patients with CRC: low intratumoral neutrophil, n = 66; high intratumoral neutrophil, n = 63. (E) pN0, probability of survival of pN0 patients with CRC: low intratumoral neutrophil, n = 96; high intratumoral neutrophil, n = 73. (F) pN1, probability of survival of pN1 patients with CRC: low intratumoral neutrophil, n = 29; high intratumoral neutrophil, n = 31.
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