title: Tumor necrosis correlates with angiogenesis and is a predictor of poor prognosis in malignant mesothelioma.
abstract: OBJECTIVE
  Malignant mesothelioma (MM) is a fatal tumor of increasing incidence related to asbestos exposure. Microscopic tumor necrosis (TN) is a poor prognostic factor in solid tumors, but it has not been characterized in MM. We wished to evaluate the incidence of TN in MM and its correlations with clinicopathologic factors, angiogenesis, and survival.
  
  
  METHODS
  TN was graded in 171 routine formalin-fixed, paraffin-embedded hematoxylin-eosin-stained tumor sections by two independent observers. Angiogenesis was assessed by the microvessel count (MVC) of CD34 immunostained sections. TN was correlated with survival by Kaplan-Meier and log-rank analysis, and stepwise, multivariate Cox models were used to compare TN with angiogenesis and established prognostic factors and prognostic scoring systems.
  
  
  RESULTS
  TN was identified in 39 cases (22.8%) and correlated with low hemoglobin (p = 0.01), thrombocytosis (p = 0.04), and high MVC (p = 0.02). TN was a poor prognostic factor in univariate analysis (p = 0.008). Patients with TN had a median survival of 5.3 months vs 8.3 months in negative cases. Independent indicators of poor prognosis in multivariate analysis were nonepithelioid cell type (p = 0.0001), performance status > 0 (p = 0.007), and increasing MVC (p = 0.004) but not TN. TN contributed independently to the European Organisation for Research and Treatment of Cancer (EORTC) [p = 0.03] and to the Cancer and Leukemia Group B (CALGB) [p = 0.03] prognostic groups in respective multivariate Cox analyses.
  
  
  CONCLUSIONS
  TN correlates with angiogenesis and is a poor prognostic factor in MM. TN contributes to the EORTC and CALGB prognostic scoring systems.
authors: Department of Oncology, University of Leicester, Leicester, UK.
authors: John G
authors: JG
authors: Edwards
authors: Daniel E B
authors: DE
authors: Swinson
authors: J Louise
authors: JL
authors: Jones
authors: Salli
authors: S
authors: Muller
authors: David A
authors: DA
authors: Waller
authors: Kenneth J
authors: KJ
authors: O'Byrne
mesh_terms: D005260:Female; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000098:blood supply / Q000401:mortality / Q000473:pathology*; D008875:Middle Aged; D015999:Multivariate Analysis; D009336:Necrosis; D009389:Neovascularization, Pathologic / Q000473:pathology*; D010997:Pleural Neoplasms / Q000098:blood supply / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D015996:Survival Rate