肺腺癌巨噬细胞M2表型边缘极化效应观察及预后分析

目的:探讨肺腺癌边缘区巨噬细胞M2表型的极化效应、边缘/中心比值及对预后的影响。方法:采用双重免疫组化技术,观察巨噬细胞CD163+/CD68+表型(M2表型)在49例原位肺腺癌(AIS)、11例微小浸润性腺癌(MIA)、57例浸润性腺癌(IA)边缘区及中心区的分布规律和差异,探讨巨噬细胞边缘极化效应及边缘/中心比值在肺腺癌进程中的作用及机制。采用单因素Kaplan-Meier生存曲线分析及多变量Cox生存分析探讨M2表型边缘极化状态与预后的关系。结果:肺腺癌边缘区M2型巨噬细胞较中心区域呈现极性聚集,具有显著差异(P0.01)。根据中位数分高、低极化组,低极化组AIS中M2型巨噬细胞计数值与MIA及IA比较未见明显差别,但其在高、极化组AIS中的计数值依次低于MIA和IA,差异有统计学意义(均P0.01)。单因素Kaplan-Meier生存曲线分析及log-rank检验结果显示边缘区巨噬细胞M2表型数量及边缘/中心比值与生存时间呈负相关(2=44.71,P0.01;2=21.75,P0.01)。多变量Cox生存分析表明M2表型边缘高极化状态和边缘/中心比值是独立的预后危险因素(P0.01)。结论:巨噬细胞M2表型在肺腺癌边缘区存在边缘极化效应,其边缘极化状态和边缘/中心比值是独立的预后危险因素,因此术前穿刺判断边缘极化状态或术后活检检测M2型巨噬细胞型边缘/中心比值可能是评估预后的一种有效方法。

Polarized distribution of M2 macrophages in marginal region around lung adenocarcinoma and its effect on prognosis

AIM: To explore the polarized distribution of M2 macrophages in the marginal region around lung adenocarcinoma, the marginal/central ratio and their effect on the prognosis. METHODS: Double immunohistochemistry staining was used to determine the distribution and the difference of CD163⁺/CD68⁺ (M2) macrophages in the marginal and central regions in 49 cases of lung adenocarcinoma in situ (AIS), 11 cases of minimally invasive adenocarcinoma (MIA) and 57 cases of invasive adenocarcinoma (IA) in order to explore the effect and mechanism of the polarized distribution and the marginal/central ratio on the progression of lung adenocarcinoma. Single-factor Kaplan-Meier survival curve analysis and multivariate Cox survival analysis were employed to explore the relationship between the polarized distribution of M2 macrophages and the prognosis. RESULTS: Polarized aggregation of M2 macrophages was observed in the marginal region of lung adenocarcinoma compared with that in the central region, and the difference was significant (P<0.01). Based on the median level, they were divided into high polarized group and low polarized group. In low polarized group, M2 macrophage count in AIS was not significantly different from that in MIA or IA. However, in high polarized group, M2 macrophage count in AIS was lower than that in MIA and IA in turn and there were statistically significant differences (P<0.01). Single-factor Kaplan-Meier survival curve analysis and log-rank test result showed that the number of M2 macrophages in the marginal region and marginal/central ratio were negatively correlated to the survival time (χ²=44.71, P<0.01; χ²=21.75, P<0.01). Multivariate Cox survival analysis showed that the high polarized distribution of M₂ macrophages in the marginal region and the marginal/central ratio were independent risk factors for the prognosis (P<0.01). CONCLUSION: There is a polarization effect of M2 macrophages on the marginal region of lung adenocarcinoma. The marginal polarization and the marginal/central ratio are independent risk factors of the prognosis. Therefore, it may be an effective method for the evaluation of the prognosis to judge the marginal polarization by preoperative puncture and to determine the marginal/central ratio of M2 macrophages by postoperative biopsy.