Rakaee Mehrdad, Busund Lill-Tove, Paulsen Erna-Elise, Richardsen Elin, Al-Saad Samer, Andersen Sigve, Donnem Tom, Bremnes Roy M, Kilvaer Thomas K
Department of Medical Biology, University of Tromsø, The Arctic University of Norway, N-9037 Tromso, Norway.
Department of Clinical Pathology, University Hospital of North Norway, N-9038 Tromso, Norway.
Oncotarget. 2016 Nov 1;7(44):72184-72196. doi: 10.18632/oncotarget.12360.
Recent data indicate that tumor-associated neutrophils (TANs) serve a dual role in tumor progression and regression. CD66b is a neutrophil marker and has been associated with patient outcome in various cancers. However, its clinical impact in non-small cell lung cancer (NSCLC) remains controversial. 536 NSCLC patients, of which 172 harbored lymph node metastases, were included in this study. Tissue microarrays were constructed and multiplexed immunohistochemistry of CD66b, CD34 and pan-keratin was performed to evaluate the localization and quantity of CD66b+ TANs. High intratumoral CD66b+ TANs density in squamous cell carcinoma (SCC) subgroup was an independent positive prognosticator for disease-specific survival (P = 0.038). In contrast, high intratumoral TANs density was an independent negative prognostic factor in the adenocarcinoma (ADC) subgroup (P= 0.032). Likewise, in ADC patients with lymph node metastases, high level of intratumoral TANs was associated with poor prognosis (P = 0.003). Stromal CD66b+ TANs were not associated with outcome of NSCLC patients. In conclusion, CD66b+ TANs show diverging prognostic effect in NSCLC patients according to histological subgroups. The presence of CD66b+ TANs could prove pivotal for development of an immunoscore in ADC NSCLC patients.
近期数据表明，肿瘤相关中性粒细胞（TANs）在肿瘤进展和消退中发挥双重作用。CD66b是一种中性粒细胞标志物，与多种癌症患者的预后相关。然而，其在非小细胞肺癌（NSCLC）中的临床影响仍存在争议。本研究纳入了536例NSCLC患者，其中172例有淋巴结转移。构建组织微阵列并进行CD66b、CD34和全角蛋白的多重免疫组化，以评估CD66b+TANs的定位和数量。鳞状细胞癌（SCC）亚组中肿瘤内CD66b+TANs高密度是疾病特异性生存的独立阳性预后因素（P = 0.038）。相比之下，腺癌（ADC）亚组中肿瘤内TANs高密度是独立的阴性预后因素（P = 0.032）。同样，在有淋巴结转移的ADC患者中，肿瘤内TANs高水平与预后不良相关（P = 0.003）。基质CD66b+TANs与NSCLC患者的预后无关。总之，根据组织学亚组，CD66b+TANs在NSCLC患者中显示出不同的预后作用。CD66b+TANs 的存在可能对ADC NSCLC患者免疫评分的发展至关重要。
