title: Prognostic effect of intratumoral neutrophils across histological subtypes of non-small cell lung cancer.
abstract: 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.
authors.affiliation: Department of Medical Biology,  University of Tromsø, The Arctic University of Norway, N-9037 Tromso, Norway.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Rakaee
authors.affiliation: 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.
authors.forename: Lill-Tove
authors.initials: LT
authors.lastname: Busund
authors.affiliation: Department of Clinical Medicine,  University of Tromsø, The Arctic University of Norway, N-9037 Tromso, Norway.|Department of Oncology, University Hospital of North Norway, N-9038 Tromso, Norway.
authors.forename: Erna-Elise
authors.initials: EE
authors.lastname: Paulsen
authors.affiliation: 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.
authors.forename: Elin
authors.initials: E
authors.lastname: Richardsen
authors.affiliation: 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.
authors.forename: Samer
authors.initials: S
authors.lastname: Al-Saad
authors.affiliation: Department of Clinical Medicine,  University of Tromsø, The Arctic University of Norway, N-9037 Tromso, Norway.|Department of Oncology, University Hospital of North Norway, N-9038 Tromso, Norway.
authors.forename: Sigve
authors.initials: S
authors.lastname: Andersen
authors.affiliation: Department of Clinical Medicine,  University of Tromsø, The Arctic University of Norway, N-9037 Tromso, Norway.|Department of Oncology, University Hospital of North Norway, N-9038 Tromso, Norway.
authors.forename: Tom
authors.initials: T
authors.lastname: Donnem
authors.affiliation: Department of Clinical Medicine,  University of Tromsø, The Arctic University of Norway, N-9037 Tromso, Norway.|Department of Oncology, University Hospital of North Norway, N-9038 Tromso, Norway.
authors.forename: Roy M
authors.initials: RM
authors.lastname: Bremnes
authors.affiliation: Department of Clinical Medicine,  University of Tromsø, The Arctic University of Norway, N-9037 Tromso, Norway.|Department of Oncology, University Hospital of North Norway, N-9038 Tromso, Norway.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Kilvaer
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D018450:Disease Progression; D004848:Epithelium / Q000378:metabolism; D005260:Female; D058851:GPI-Linked Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D011379:Prognosis; D012189:Retrospective Studies; D046888:Tissue Array Analysis
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D014408:Biomarkers, Tumor; C504120:CEACAM8 protein, human; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins
keywords: CD66b; NSCLC; TANs; lung cancer; neutrophils