title: The presence of intraepithelial CD45RO+ cells in resected lymph nodes with metastases from NSCLC patients is an independent predictor of disease-specific survival.
abstract: Operable non-small cell lung cancer (NSCLC) patients whose tumours have spread to regional or central lymph nodes at the time of diagnosis have dismal prognoses compared with those who have limited disease. The current TNM staging system for NSCLC poorly distinguishes patients with lymph-node metastases who will succumb to, and those who will eventually be cured from, their disease. This novel study: (1) evaluates the presence of different subsets of intraepithelial tumour-infiltrating lymphocytes (TILs) in lymph nodes with metastases from NSCLC patients; (2) explores the impact of intraepithelial TILs in lymph nodes on survival; (3) correlates their presence with both intraepithelial and stromal TILs in their corresponding primary tumours.
  
  
  
  Metastatic lymph-node tissue from 143N+ NSCLC patients was collected and tissue microarrays were constructed. Immunohistochemistry was used to evaluate the presence of intraepithelial CD3+, CD4+, CD8+, CD20+ and CD45RO+ TILs and their impact on survival.
  
  
  
  A high level of intraepithelial CD45RO+ TILs in lymph-node metastases from N+ NSCLC patients was an independent positive prognostic factor for disease-specific survival in all patients (HR=0.58, P=0.029) and in squamous cell carcinoma (HR=0.31, P=0.006), but not in adenocarcinoma patients.
  
  
  
  The presence of intraepithelial CD45RO+ cells in lymph-node metastases from N+ NSCLC patients predicts favourable disease-specific survival and outperforms the established TNM staging system in the SCC subgroup.
authors.affiliation: Department of Oncology, University Hospital of North Norway, Tromso, Norway.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Kilvaer
authors.affiliation: Department of Oncology, University Hospital of North Norway, Tromso, Norway.|Institute of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway.
authors.forename: Erna-Elise
authors.initials: EE
authors.lastname: Paulsen
authors.affiliation: Institute of Medical Biology, UiT The Arctic University of Norway, Tromso, Norway.
authors.forename: Mehrdad R
authors.initials: MR
authors.lastname: Khanehkenari
authors.affiliation: Institute of Medical Biology, UiT The Arctic University of Norway, Tromso, Norway.|Department of Clinical Pathology, University Hospital of North Norway, Tromso, Norway.
authors.forename: Samer
authors.initials: S
authors.lastname: Al-Saad
authors.affiliation: Department of Pathology, Nordland Hospital, Bodo, Norway.
authors.forename: Ramona M
authors.initials: RM
authors.lastname: Johansen
authors.affiliation: Department of Pathology, Nordland Hospital, Bodo, Norway.
authors.forename: Khalid
authors.initials: K
authors.lastname: Al-Shibli
authors.affiliation: Department of Oncology, University Hospital of North Norway, Tromso, Norway.|Institute of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway.
authors.forename: Roy M
authors.initials: RM
authors.lastname: Bremnes
authors.affiliation: Institute of Medical Biology, UiT The Arctic University of Norway, Tromso, Norway.|Department of Clinical Pathology, University Hospital of North Norway, Tromso, Norway.
authors.forename: Lill-Tove
authors.initials: LT
authors.lastname: Busund
authors.affiliation: Department of Oncology, University Hospital of North Norway, Tromso, Norway.|Institute of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway.
authors.forename: Tom
authors.initials: T
authors.lastname: Donnem
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology*; D002294:Carcinoma, Squamous Cell / Q000276:immunology; D005260:Female; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D008175:Lung Neoplasms / Q000276:immunology*; D008197:Lymph Node Excision; D008207:Lymphatic Metastasis; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis; D046888:Tissue Array Analysis / Q000379:methods*
chemical_list: D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human