Effect Of Tumor-associated Macrophages On Endometrioid Adenocarcinoma

ObjectivesAccording to researches abroad in recent years, tumor-asscoated macrophages (TAMs), those macrophages distributed in tumors, might play a crucial role in tumor carcinogenesis, progression, invasion and metastases. This experiment was to explore the correlations of TAMs to clinicopathologic features, matrix metalloproteinase-2 (MMP-2) and microvessel density (MVD) in endometrioid adenocarcinoma, and focus on discussing the effect of TAMs on endometrial carcinoma invasion, metastases and angiogenesis. In addtion, the correlations of TAMs to estrogen receptor (ER) and progesterone receptor (PR) expression in endometrioid adenocarcinoma was discussed initially.Methods67 cases of endometrioid adenocarcinoma underwent panhysterectomy at Tianjin Medical University General Hospital between 2003 and 2007 were retrospectively retrieved. Two-step immunohistochemical staining was used to detect CD68, MMP-2, CD34, ER and PR expression in endometrioid adenocarcinoma. CD68 was the marker of TAMs and CD34 was the marker of MVD in this experiment. Tumor was divided into two regions, tumor tissues and margin tissues with tumor invasion. Thus statistics of markers were done respectively in these two regions. All statistical analyses were performed using the statistical package SPSS 15.0, including two independent samples t test and Mann-Whitney U test, chi-square test and correlation analysis, and Spearman correlation analysis. Significance level a was 0.05.Results1.TAMs were scattered, focal, or tableted distributing in tumor tissues and margin tissues with tumor invasion. TAMs were observed in 65 cases(97.0%) of tumor tissues and 61 cases(91.0%) of margin tissues respectively, and the number of margin TAMs was more than margin TAMs with statistical significance(P<0.001). Both of the number of margin TAMs and intratumor TAMs were significantly more in cases with invasing myometrium≥1/2 than invasing myometrium<1/2 and preinvasive cases (P=0.035,P=0.025), and the number of margin TAMs was significantly more in cases with pelvic lymph node metastases (P=0.001).2.MMP-2 positive mainly expressed in cancer cell cytoplasm in endometrioid adenocarcinoma. MMP-2 positive rate was 49.3%(33/67) in tumor tissues, and 58.2%(39/67) in margin tissues, and the former was lower than the latter with statistical significance(P<0.001).Intratumor MMP-2 positive rate was significantly higher in elder patients(P=0.012), and in cases with higher FIGO stage(P<0.001), and with pelvic lymph node metastases(P<0.001).Margin MMP-2 positive rate was significantly higher in cases with higher pathology grade(P=0.007), with invasing myometrium≥1/2 (P=0.041).In margin tissues, the number of margin TAMs with MMP-2 positive was more than MMP-2 negative with statistical significance (P=0.014).3.CD34 positive cells located any region in tumor stroma. There was no statistical difference between intratumor MVD and margin MVD(P=0.643). Intratumor MVD were significantly higher in cases with invasing myometrium≥1/2 (P=0.048), and margin MVD were significantly higher in cases with lower pathology grade(P=0.031),with invasing myometrium≥1/2 (P=0.014). There was a positive correlation between the number of intatumor MVD and intratumor TAMs (P=0.003).4. In tumor tissues and margin tissues,there was no statistical difference of the number of TAMs between ER positive and ER negative, and there was no statistical difference of the number of TAMs between PR positive and PR negative (P>0.05).Conclusions1.TAMs were significantly more in cases with invasing myometrium≥1/2 and pelvic lymph node metastases in endometrioid adenocarcinoma. TAMs maybe enhance invasiveness of tumor cells and affect endometrioid adenocarcinoma myometrium invasion and metastases.2.Tumor cells, specially in margin tissues, increased expression of MMP-2 was correlated to increased invasiveness of endometrioid adenocarcinoma. In margin tissues, the number of margin TAMs with MMP-2 positive was more than MMP-2 negative, so the interaction between tumor cells and TAMs maybe influence on tumor cells expressing MMP-2. 3.Through the autocrine and paracrine pathway, TAMs might be release a number of growth factors including proangiogensis cytokines to modulate angiogenesis in endometrioid adenocarcinoma.4. The correlations between the number of TAMs and the expression of ER/PR in endometrioid adenocarcinoma has not been detected in this experiment.