Department of Cellular and Organ Pathology, Graduate School of Medicine, Akita University, 1-1-1 Hondo, Akita City, Akita, 010-8543, Japan; Department of Laboratory Medicine, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi, 710077, PR China.
Department of Cellular and Organ Pathology, Graduate School of Medicine, Akita University, 1-1-1 Hondo, Akita City, Akita, 010-8543, Japan.
Lung Cancer. 2018 Sep;123:127-135. doi: 10.1016/j.lungcan.2018.07.015. Epub 2018 Jul 19.
Tumor-associated macrophages (TAMs) are believed to influence tumor progression and the prognosis of patients. The purpose of this study was to clarify the correlation between the TAM density or location and the clinicopathological features of non-small-cell lung cancer (NSCLC) as well as to explore the prognostic impact of TAMs in NSCLC.
CD68- and CD204-positive macrophages were detected in tumor islets, tumor stroma and alveolar space in 297 patients with NSCLC using immunochemistry. The clinicopathological and genetic factors surveyed were the disease-free survival, age, gender, smoking status, histological type, disease stage, histological grade, pleural invasion, lymph node metastasis, EGFR gene mutations and ALK rearrangements.
There were significantly more CD68-positive macrophages than CD204-positive macrophages in each location of the tumor islets, tumor stroma and alveolar spaces, and they were strongly correlated (P < 0.0001 each). Factors such as male gender, being a smoker, an advanced disease stage and histological grade, positive pleural invasion and node status and wild-type EGFR gene status were significantly correlated with a higher density of CD68- and CD204-positive TAMs in tumor stroma (P < 0.05 each). In contrast, the age of patients was not correlated with CD68- and CD204-positive TAMs (P > 0.05 each). Furthermore, survival analysis revealed that a high number of CD68- and CD204-positive TAMs in tumor stroma, but not in tumor islets or alveolar space, was a significant prognostic factor for the disease-free survival time of NSCLC (P < 0.05, respectively). Moreover, both univariate and multivariate analyses confirmed that higher numbers of CD204-positive TAMs in tumor stroma were an independent worse prognostic predictor for adenocarcinoma.
The tumor stroma is the most suitable intratumoral area for the evaluation of TAMs in the setting of the prognostic prediction of NSCLC patients. CD204-positive TAMs are the preferable marker for prognostic prediction in NSCLC, especially in lung adenocarcinoma.
肿瘤相关巨噬细胞（TAMs）被认为会影响肿瘤的进展和患者的预后。本研究旨在阐明 TAM 密度或位置与非小细胞肺癌（NSCLC）的临床病理特征之间的相关性，并探讨 TAMs 在 NSCLC 中的预后影响。
采用免疫组织化学法检测 297 例 NSCLC 患者肿瘤岛、肿瘤基质和肺泡腔中 CD68 和 CD204 阳性巨噬细胞。调查的临床病理和遗传因素包括无病生存期、年龄、性别、吸烟状况、组织学类型、疾病分期、组织学分级、胸膜侵犯、淋巴结转移、EGFR 基因突变和 ALK 重排。
在肿瘤岛、肿瘤基质和肺泡腔的每个部位，CD68 阳性巨噬细胞的数量明显多于 CD204 阳性巨噬细胞，且两者呈强相关性（均 P<0.0001）。男性、吸烟、晚期疾病分期和组织学分级、阳性胸膜侵犯和淋巴结状态以及野生型 EGFR 基因突变状态等因素与肿瘤基质中 CD68 和 CD204 阳性 TAMs 的密度显著相关（均 P<0.05）。相反，患者的年龄与 CD68 和 CD204 阳性 TAMs 无相关性（均 P>0.05）。此外，生存分析显示，肿瘤基质中大量 CD68 和 CD204 阳性 TAMs 是 NSCLC 无病生存时间的显著预后因素（均 P<0.05）。此外，单因素和多因素分析均证实，肿瘤基质中 CD204 阳性 TAMs 数量较高是腺癌患者独立的预后不良预测指标。
在预测 NSCLC 患者预后方面，肿瘤基质是评估 TAMs 的最适合的肿瘤内区域。CD204 阳性 TAMs 是 NSCLC 预后预测的更优标志物，尤其是在肺腺癌中。
