title: Angiogenesis and molecular biologic substaging in patients with stage I non-small cell lung cancer.
abstract: BACKGROUND
  Although complete surgical resection remains the primary treatment for localized stage I non-small cell lung cancer, the cancer recurrence rate is 25% to 40%. If one could identify, a subset of patients using molecular factors that contribute to tumour aggressiveness, one might improve prognosis in this group with additional treatment. High expression of angiogenesis factor viii has been associated with the presence of nodal metastases in breast cancer; here we examined its relation to survival with non-small lung cancer.
  
  
  METHODS
  We examined angiogenesis using immunohistochemistry on paraffin blocks of tumour from 275 consecutive patients with stage I non-small cell lung cancer, more than 68 months of follow-up, and a 64% 5-year survival. Angiogenesis was calculated from the microvessel number per ten 200 x microscope fields measured at the tumor periphery, in the center, and in the area of highest concentration.
  
  
  RESULTS
  Measurements in the central area were inconsistent due to prominent necrosis. However, microvessel number recorded at the periphery and at the "hottest" are correlated well (r2 = 0.952; p = 0.001), and a significant survival advantage was noted for low-level expression at both areas (peripheral, p = 0.046; "hottest", p = 0.006). Multivariate survival analysis using angiogenesis, protooncogene erbB-2, tumor suppressor gene p53, and the proliferation marker KI-67 defined angiogenesis as the most significant prognostic factor in stage I lung cancer.
  
  
  CONCLUSIONS
  This molecular biologic substaging system including angiogenesis for stage I non-small cell lung cancer is independent of routine histopathologic factors and revealed an additive adverse effect with expression of several biologic markers (5-year survival: no marker [n = 51] 81%, 1 marker [n = 82] 71%, 2 markers [n = 84] 54%, and 3 to 4 markers [n = 58] 49%; p = 0.0001).
authors.affiliation: Lung Cancer Research Laboratory, Dana Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Harpole
authors.forename: W G
authors.initials: WG
authors.lastname: Richards
authors.forename: J E
authors.initials: JE
authors.lastname: Herndon
authors.forename: D J
authors.initials: DJ
authors.lastname: Sugarbaker
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D043925:Angiogenesis Inducing Agents / Q000032:analysis; D014408:Biomarkers, Tumor; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply* / Q000737:chemistry / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply* / Q000737:chemistry / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D016612:Paraffin Embedding; D016019:Survival Analysis
chemical_list: D043925:Angiogenesis Inducing Agents; D014408:Biomarkers, Tumor