title: Tumour necrosis is an independent prognostic marker in non-small cell lung cancer: correlation with biological variables.
abstract: BACKGROUND
  Tumour necrosis (TN) is recognized to be a consequence of chronic cellular hypoxia. TN and hypoxia correlate with poor prognosis in solid tumours.
  
  
  METHODS
  In a retrospective study the prognostic implications of the extent of TN was evaluated in non-small cell lung cancer (NSCLC) and correlated with clinicopathological variables and expression of epidermal growth factor receptor, Bcl-2, p53 and matrix metalloproteinase-9 (MMP-9). Tissue specimens from 178 surgically resected cases of stage I-IIIA NSCLC with curative intent were studied. The specimens were routinely processed, formalin-fixed and paraffin-embedded. TN was graded as extensive or either limited or absent by two independent observers; disagreements were resolved using a double-headed microscope. The degree of reproducibility was estimated by re-interpreting 40 randomly selected cases after a 4 month interval.
  
  
  RESULTS
  Reproducibility was attained in 36/40 cases, Kappa score = 0.8 P < 0.001. TN correlated with T-stage (P = 0.001), platelet count (P = 0.004) and p53 expression (P = 0.031). Near significant associations of TN with N-stage (P = 0.063) and MMP-9 expression (P = 0.058) were seen. No association was found with angiogenesis (P = 0.98). On univariate (P = 0.0016) and multivariate analysis (P = 0.023) TN was prognostic.
  
  
  CONCLUSIONS
  These results indicate that extensive TN reflects an aggressive tumour phenotype in NSCLC and may improve the predictive power of the TMN staging system. The lack of association between TN and angiogenesis may be important although these variables were not evaluated on serial sections.
authors.affiliation: Department of Oncology, University Hospitals of Leicester NHS Trust, Leicester LE1 5WW, UK.
authors.forename: Daniel E B
authors.initials: DE
authors.lastname: Swinson
authors.forename: J Louise
authors.initials: JL
authors.lastname: Jones
authors.forename: Donna
authors.initials: D
authors.lastname: Richardson
authors.forename: Giles
authors.initials: G
authors.lastname: Cox
authors.forename: John G
authors.initials: JG
authors.lastname: Edwards
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: O'Byrne
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010641:Phenotype; D010976:Platelet Count; D011379:Prognosis; D015203:Reproducibility of Results; D012189:Retrospective Studies; D013534:Survival; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
chemical_list: D014408:Biomarkers, Tumor; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53