Department of Surgery, University Hospital Basel, Switzerland.
PLoS One. 2013 May 29;8(5):e64814. doi: 10.1371/journal.pone.0064814. Print 2013.
Colorectal cancer (CRC) infiltration by adaptive immune system cells correlates with favorable prognosis. The role of the innate immune system is still debated. Here we addressed the prognostic impact of CRC infiltration by neutrophil granulocytes (NG).
A TMA including healthy mucosa and clinically annotated CRC specimens (n = 1491) was stained with MPO and CD15 specific antibodies. MPO+ and CD15+ positive immune cells were counted by three independent observers. Phenotypic profiles of CRC infiltrating MPO+ and CD15+ cells were validated by flow cytometry on cell suspensions derived from enzymatically digested surgical specimens. Survival analysis was performed by splitting randomized data in training and validation subsets.
MPO+ and CD15+ cell infiltration were significantly correlated (p<0.0001; r = 0.76). However, only high density of MPO+ cell infiltration was associated with significantly improved survival in training (P = 0.038) and validation (P = 0.002) sets. In multivariate analysis including T and N stage, vascular invasion, tumor border configuration and microsatellite instability status, MPO+ cell infiltration proved an independent prognostic marker overall (P = 0.004; HR = 0.65; CI:±0.15) and in both training (P = 0.048) and validation (P = 0.036) sets. Flow-cytometry analysis of CRC cell suspensions derived from clinical specimens showed that while MPO+ cells were largely CD15+/CD66b+, sizeable percentages of CD15+ and CD66b+ cells were MPO-.
High density MPO+ cell infiltration is a novel independent favorable prognostic factor in CRC.
适应性免疫系统细胞浸润结直肠癌（CRC）与预后良好相关。先天免疫系统的作用仍存在争议。在这里，我们研究了中性粒细胞（NG）浸润 CRC 的预后影响。
使用 MPO 和 CD15 特异性抗体对包括健康黏膜和临床注释 CRC 标本的 TMA 进行染色（n=1491）。由三位独立观察者对 MPO+和 CD15+阳性免疫细胞进行计数。通过对来自酶消化手术标本的细胞悬浮液进行流式细胞术验证 CRC 浸润 MPO+和 CD15+细胞的表型谱。通过将随机数据分割为训练和验证子集来进行生存分析。
MPO+和 CD15+细胞浸润显著相关（p<0.0001；r=0.76）。然而，仅高密度的 MPO+细胞浸润与训练（P=0.038）和验证（P=0.002）集的生存率显著提高相关。在包括 T 和 N 期、血管侵犯、肿瘤边界形态和微卫星不稳定性状态的多变量分析中，MPO+细胞浸润总体上证明是独立的预后标志物（P=0.004；HR=0.65；CI：±0.15），并且在训练（P=0.048）和验证（P=0.036）集均如此。从临床标本中获得的 CRC 细胞悬浮液的流式细胞术分析表明，虽然 MPO+细胞主要是 CD15+/CD66b+，但相当大比例的 CD15+和 CD66b+细胞是 MPO-。
高密度 MPO+细胞浸润是 CRC 的一种新的独立有利预后因素。
