非小细胞肺癌中肿瘤相关巨噬细胞的 M1 形态与生存时间呈正相关。
The M1 form of tumor-associated macrophages in non-small cell lung cancer is positively associated with survival time.
机构信息
Department of Thoracic and Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.
出版信息
BMC Cancer. 2010 Mar 25;10:112. doi: 10.1186/1471-2407-10-112.
BACKGROUND
Tumor-associated macrophages (TAMs) play an important role in growth, progression and metastasis of tumors. In non-small cell lung cancer (NSCLC), TAMs' anti-tumor or pro-tumor role is not determined. Macrophages are polarized into M1 (with anti-tumor function) and M2 (with pro-tumor function) forms. This study was conducted to determine whether the M1 and M2 macrophage densities in NSCLC are associated with patient's survival time.
METHODS
Fifty patients with an average of 1-year survival (short survival group) and 50 patients with an average of 5-year survival (long survival group) were included in this retrospective study. Paraffin-embedded NSCLC specimens and their clinicopathological data including up to 8-year follow-up information were used. Immunohistochemical double-staining of CD68/HLA-DR (markers for M1 macrophages) and CD68/CD163 (markers for M2 macrophages) was performed and evaluated in a blinded fashion. The M1 and M2 macrophage densities in the tumor islets, stroma, or islets and stroma were determined using computer-aided microscopy. Correlation of the macrophage densities and patient's survival time was analyzed using the Statistical Package for the Social Sciences.
RESULTS
Approximately 70% of TAMs were M2 macrophages and the remaining 30% were M1 macrophages in NSCLC. The M2 macrophage densities (approximately 78 to 113 per mm2) in the tumor islets, stroma, or islets and stroma were not significantly different between the long survival and short survival groups. The M1 macrophage densities in the tumor islets (approximately 70/mm2) and stroma (approximately 34/mm2) of the long survival group were significantly higher than the M1 macrophage densities in the tumor islets (approximately 7/mm2) and stroma (13/mm2) of the short survival group (P < 0.001 and P < 0.05, respectively). The M2 macrophage densities were not associated with patient's survival time. The M1 macrophage densities in the tumor islets, stroma, or islets and stroma were positively associated with patient's survival time in a univariate analysis (P < 0.01 or 0.001). In a multivariate Cox proportional hazards analysis, the M1 macrophage density in the tumor islets was an independent predictor of patient's survival time.
CONCLUSIONS
The M1 macrophage density in the tumor islets is an independent predictor of survival time in NSCLC patients.
背景
肿瘤相关巨噬细胞（TAMs）在肿瘤的生长、进展和转移中起着重要作用。在非小细胞肺癌（NSCLC）中，TAMs 的抗肿瘤或促肿瘤作用尚未确定。巨噬细胞可极化为 M1（具有抗肿瘤功能）和 M2（具有促肿瘤功能）两种形式。本研究旨在确定 NSCLC 中 M1 和 M2 巨噬细胞密度是否与患者的生存时间有关。
方法
本回顾性研究纳入了平均生存时间为 1 年（短期生存组）的 50 例患者和平均生存时间为 5 年（长期生存组）的 50 例患者。使用石蜡包埋的 NSCLC 标本及其临床病理资料，包括长达 8 年的随访信息。采用 CD68/HLA-DR（M1 巨噬细胞标志物）和 CD68/CD163（M2 巨噬细胞标志物）免疫组织化学双重染色，并进行盲法评估。使用计算机辅助显微镜测定肿瘤岛、基质或肿瘤岛和基质中 M1 和 M2 巨噬细胞的密度。使用社会科学统计软件包分析巨噬细胞密度与患者生存时间的相关性。
结果
在 NSCLC 中，约 70%的 TAMs 为 M2 巨噬细胞，其余 30%为 M1 巨噬细胞。长期生存组和短期生存组肿瘤岛、基质或肿瘤岛和基质中 M2 巨噬细胞密度（约 78 至 113 个/mm2）无显著差异。长期生存组肿瘤岛（约 70/mm2）和基质（约 34/mm2）中的 M1 巨噬细胞密度明显高于短期生存组肿瘤岛（约 7/mm2）和基质（13/mm2）中的 M1 巨噬细胞密度（P<0.001 和 P<0.05）。M2 巨噬细胞密度与患者生存时间无关。单因素分析显示，肿瘤岛、基质或肿瘤岛和基质中的 M1 巨噬细胞密度与患者生存时间呈正相关（P<0.01 或 0.001）。多因素 Cox 比例风险分析显示，肿瘤岛中 M1 巨噬细胞密度是患者生存时间的独立预测因子。
结论
肿瘤岛中 M1 巨噬细胞密度是 NSCLC 患者生存时间的独立预测因子。
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