CD163、VEGF、HLA-DR、iNOS 和 MRP 8/14 的组织微定位和细胞表达与 NSCLC 的临床结果相关。

The tissue microlocalisation and cellular expression of CD163, VEGF, HLA-DR, iNOS, and MRP 8/14 is correlated to clinical outcome in NSCLC.

机构信息

Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom.

出版信息

PLoS One. 2011;6(7):e21874. doi: 10.1371/journal.pone.0021874. Epub 2011 Jul 22.

BACKGROUND

We have previously investigated the microlocalisation of M1 and M2 macrophages in NSCLC. This study investigated the non-macrophage (NM) expression of proteins associated with M1 and M2 macrophages in NSCLC.

METHODS

Using immunohistochemistry, CD68(+) macrophages and proteins associated with either a cytotoxic M1 phenotype (HLA-DR, iNOS, and MRP 8/14), or a non-cytotoxic M2 phenotype (CD163 and VEGF) were identified. NM expression of the markers was analysed in the islets and stroma of surgically resected tumours from 20 patients with extended survival (ES) (median 92.7 months) and 20 patients with poor survival (PS) (median 7.7 months).

RESULTS

The NM expression of NM-HLA-DR (p<0.001), NM-iNOS (p = 0.02) and NM-MRP 8/14 (p = 0.02) was increased in ES compared to PS patients in the tumour islets. The tumour islet expression of NM-VEGF, was decreased in ES compared to PS patients (p<0.001). There was more NM-CD163 expression (p = 0.04) but less NM-iNOS (p = 0.002) and MRP 8/14 (p = 0.01) expression in the stroma of ES patients compared with PS patients. The 5-year survival for patients with above and below median NM expression of the markers in the islets was 74.9% versus 4.7% (NM-HLA-DR p<0.001), 65.0% versus 14.6% (NM-iNOS p = 0.003), and 54.3% versus 22.2% (NM-MRP 8/14 p = 0.04), as opposed to 34.1% versus 44.4% (NM-CD163 p = 0.41) and 19.4% versus 59.0% (NM-VEGF p = 0.001).

CONCLUSIONS

Cell proteins associated with M1 and M2 macrophages are also expressed by other cell types in the tumour islets and stroma of patients with NSCLC. Their tissue and cellular microlocalisation is associated with important differences in clinical outcome.

背景

我们之前研究了非小细胞肺癌（NSCLC）中 M1 和 M2 巨噬细胞的微定位。本研究调查了 NSCLC 中非巨噬细胞（NM）表达与 M1 和 M2 巨噬细胞相关的蛋白。

方法

使用免疫组织化学，鉴定 CD68（+）巨噬细胞和与细胞毒性 M1 表型（HLA-DR、iNOS 和 MRP8/14）或非细胞毒性 M2 表型（CD163 和 VEGF）相关的蛋白。在来自 20 名生存时间延长（ES）（中位数 92.7 个月）和 20 名生存时间差（PS）（中位数 7.7 个月）患者的手术切除肿瘤的胰岛和基质中分析标记物的 NM 表达。

结果

与 PS 患者相比，ES 患者肿瘤胰岛中 NM-HLA-DR（p<0.001）、NM-iNOS（p=0.02）和 NM-MRP8/14（p=0.02）的 NM 表达增加。与 PS 患者相比，ES 患者肿瘤胰岛中 NM-VEGF 的表达降低（p<0.001）。ES 患者的肿瘤基质中 NM-CD163 表达增加（p=0.04），而 NM-iNOS（p=0.002）和 MRP8/14（p=0.01）表达减少。与标记物的 NM 表达中位数以上的患者相比，标记物的 NM 表达中位数以下的患者的 5 年生存率分别为 74.9%和 4.7%（NM-HLA-DR，p<0.001）、65.0%和 14.6%（NM-iNOS，p=0.003）和 54.3%和 22.2%（NM-MRP8/14，p=0.04），而 NM-CD163 为 34.1%和 44.4%（p=0.41）和 19.4%和 59.0%（NM-VEGF，p=0.001）。