title: Interstitial tumor-associated macrophages combined with tumor-derived colony-stimulating factor-1 and interleukin-6, a novel prognostic biomarker in non-small cell lung cancer.
abstract: OBJECTIVE
  Recent experimental evidence has indicated that interstitial tumor-associated macrophages (TAMs), tumor-derived macrophage colony-stimulating factor (also known as CSF-1), and interleukin-6 (IL-6) interact in the pathogenesis of malignant epithelial tumors, including lung cancer. The present study aimed to explore their relationship and prognostic significance in surgically resected non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Tissue microarray and immunohistochemistry were used to detect the expression of CSF-1, IL-6, and CD68-positive TAMs in 417 patients with NSCLC undergoing complete pulmonary resection from 2003 to 2008. Their correlations and clinicopathologic data were analyzed using chi-square testing. Their prognostic values were evaluated by univariate Kaplan-Meier survival analysis and multivariate Cox proportional hazard model analysis.
  
  
  RESULTS
  The expression of CSF-1 and IL-6 in NSCLC correlated positively with the infiltration degree of TAMs in the tumor stroma (r=0.184 and r=0.196, respectively; P<.001). The expression of both CSF-1 and IL-6 was statistically significant for survival (P<.001). Nevertheless, no such relationship was observed for CD68 in the tumor stroma (P>.05). When CSF-1 and/or IL-6 and CD68 were taken into consideration together, the result became statistically significant. Multivariate analysis showed that co-expression of CD68, CSF-1, and IL-6 remained the most significant and independent prognostic factor for survival (P<.05) but not the combinations of CSF-1 and IL-6, CD68 and CSF-1, or CD68 and IL-6 (P>.05). The 5-year survival rate in the CD68-negative and CSF-1- and IL-6-positive group was better than the rate in the CD68, CSF-1-, and IL-6-positive group (P<.05).
  
  
  CONCLUSIONS
  The combination of CD68 plus TAMs, CSF-1, and IL-6 is very likely to be a valuable independent predictor of survival in patients with NSCLC. Perhaps co-expression of CSF-1 and IL-6 induces interstitial TAMs to shift toward the tumor-promoting phenotype.
authors.affiliation: Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Lung Cancer Center, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
authors.forename: Bao-xiang
authors.initials: BX
authors.lastname: Pei
authors.affiliation: Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Lung Cancer Center, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
authors.forename: Bing-sheng
authors.initials: BS
authors.lastname: Sun
authors.affiliation: Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Lung Cancer Center, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China. Electronic address: peibaoxiangok@yahoo.com.
authors.forename: Zhen-fa
authors.initials: ZF
authors.lastname: Zhang
authors.affiliation: Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Lung Cancer Center, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
authors.forename: An-lei
authors.initials: AL
authors.lastname: Wang
authors.affiliation: Department of Esophageal Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Lung Cancer Center, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Ren
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D015850:Interleukin-6 / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D015850:Interleukin-6; D016173:Macrophage Colony-Stimulating Factor