Relationship Between The Expression Of Macrophage-Colony Stimulating Factors And The Infiltration Of The CD163+ Macrophages And Prognosis In Non-Small Cell Lung Cancer

BackgroundLung cancer is one of the most common malignance tumor,and has a high mortality in the globe world.Non-small cell lung cancer accounts for about 80% of all lung cancer.Many clinic and experiment study have suggested tumor infiltrated macrophages(TIMs) may promote the tumor invasion and matastasis. Macrophages are attracted by macrophages colony-stimulating factors(M-CSF) and induced to a phenotype which highly express CD163 and other moleculars.The objective of the present study is to evaluate relationship between the expression of macrophage-colony stimulating factors and the infiltration of the CD163+ macrophages and prognosis in non-small cell lung cancer. Materials and MethodsThe paraffin-embedded specimens from 47 patients who had undergone surgery for NSCLC at the first affiliated hospital of guangxi medical university from 2005 to 2006 were included in this study ,which contains 28 cases of males,19 cases of females,median age was 58 years(range,29 to 75 years).18 cases were stage I,5 stage II,21 stage III,3 stage IV.19 tumors were squamous,28 adenicarcinoma.7 cases were grade 1,22 grade 2,18 grade 3.Immunohistochemistry was performed to test the expression of M-CSF and infiltration of the CD163+ macrophages.The correlations between M-CSF/CD163+ macrophages and linicopathologic features and survival time were analysed by SolutionsStatistical Package for the Social Sciences(SPSS).Results1. The expression and distribution of M-CSF in NSCLCThe positive staining of M-CSF was mainly found on the cytoplasm of tumor cells or some of the bronchiole epithelial cells in the peritumoral tissues .Most of the alveolar epitheliums and stroma cells were negative ,although sporadic positive staining on lymphocyte,macrophage or plasmocyte.The M-CSF staining density in tumor was higher than in peritumoral lung tissue(0.026±0.023,0.006±0.004 P <0.05).2.The distribution of CD163+macrophages in NSCLCThe positive staining of CD163 was found on the membrane or cytoplasm of macrophages,but not on the tumor cells,lymphocytes,plasmocytes or fibroblasts. The mean member of macrophages in tumor margin(67.95±42.56)was higher than in tumor stroma(58.28±33.36), tumor nest(45.38±29.10)and peritumoral lung tissues(11.02±8.54), P <0.05.3.The correlations between M-CSF and CD163+ macrophages The M-CSF density in tumor was positively correlated with the density of CD163+ macrophages in tumor nest,tumor stroma and margin. (r=0.701, r=0.361,r=0.364,P <0.05)4.The correlations between M-CSF/CD163+ macrophages and clinicopathologic featuresThe M-CSF density in tumor was correlated with the tumor grade,the ratio of high M-CSF density (≥0.021 IOD)in poorly differentiated grade was 78% (14/18),significantly higher than well and moderate differentiated grades( 35% 10/29).The ratio of high density of CD163+ macrophage(≥70.00 /field) in tumor margin was 68%(15/22)in III+IV stages,higher than 33%(7/21)in I+II stages ,and with lymphnode metastasis was 70%(16/23),higher than without lymphnode metastasis 30%(6/20).CD163+ macrophage infiltration in tumor margin increased with the development of clinic stage and metastasis of lymphnode(χ~2=5.222,χ~2=6.702,P <0.05). In tumor nest and stroma there was no statistically significant association between CD163+ macrophages and clinicopathologic features(P>0.05).5.The correlations between M-CSF/CD163+ macrophages and survival timeThe median survival time of those patients with a high CD163+ macrophages density in tumor margin was 684 days compared to 1615 days with a low CD163+ macrpphages density, CD163+ macrophage infiltration in tumor margin increased with the reduction of patient survival time(χ~2=15.776,P <0.05).Multivariate Cox proportional harzards assumption was to used to assess that CD163+ macrophage infiltration in tumor margin may serve as potential markers for independent predicting prognosis in NSCLC. Conclusions1. There were M-CSF expression and CD163+ TIMs both in lung cancer and peritumoral lung tissues.The M-CSF expression and CD163+ TIMs in lung cancer were higher than in peritumoral lung tissues, M-CSF density in tumor was positively correlated with the density of CD163+macrophages in tumor nest,tumor stroma and margin.2. CD163+ macrophage infiltration in tumor margin may serve as potential markers for independent predicting prognosis in NSCLC.