title: Tumour necrosis factor-alpha expression in tumour islets confers a survival advantage in non-small cell lung cancer.
abstract: BACKGROUND
  The role of TNFalpha in cancer is complex with both pro-tumourigenic and anti-tumourigenic roles proposed. We hypothesised that anatomical microlocalisation is critical for its function.
  
  
  METHODS
  This study used immunohistochemistry to investigate the expression of TNFalpha in the tumour islets and stroma with respect to survival in 133 patients with surgically resected NSCLC.
  
  
  RESULTS
  TNFalpha expression was increased in the tumour islets of patients with above median survival (AMS) compared to those with below median survival (BMS)(p = 0.006), but similar in the stroma of both groups. Increasing tumour islet TNFalpha density was a favorable independent prognostic indicator (p = 0.048) while stromal TNFalpha density was an independent predictor of reduced survival (p = 0.007). Patients with high TNFalpha expression (upper tertile) had a significantly higher 5-year survival compared to patients in the lower tertile (43% versus 22%, p = 0.01). In patients with AMS, 100% of TNFalpha+ cells were macrophages and mast cells, compared to only 28% in the islets and 50% in the stroma of BMS patients (p < 0.001).
  
  
  CONCLUSIONS
  The expression of TNFalpha in the tumour islets of patients with NSCLC is associated with improved survival suggesting a role in the host anti-tumour immunological response. The expression of TNFalpha by macrophages and mast cells is critical for this relationship.
authors.affiliation: Institute for Lung Health, Glenfield Hospital, Leicester, UK. cohri@doctors.org.uk
authors.forename: Chandra M
authors.initials: CM
authors.lastname: Ohri
authors.forename: Aarti
authors.initials: A
authors.lastname: Shikotra
authors.forename: Ruth H
authors.initials: RH
authors.lastname: Green
authors.forename: David A
authors.initials: DA
authors.lastname: Waller
authors.forename: Peter
authors.initials: P
authors.lastname: Bradding
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018287:Carcinoma, Large Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D011379:Prognosis; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D014409:Tumor Necrosis Factor-alpha