ANGIOGENESIS AS A PREDICTOR OF SURVIVAL AFTER SURGICAL RESECTION FOR STAGE-I NON-SMALL-CELL LUNG-CANCER

Objectives: Some patients with surgically resected stage I non-small-c ell lung cancer eventually have metastatic disease, A histologic marke r of metastatic potential and diminished survival for stage I non-smal l-cell lung cancer may distinguish this patient population, This study evaluates the degree of angiogenesis as a predictor of cancer-related death after operation for stage I non-small-cell lung cancer, Methods : Demographic, surgical, and histopathologic data, including presence of vascular invasion, were reviewed for 106 patients,vith stage I non- small-cell lung cancer from 1985 through 1990, Visual quantitation of microvessels immunostained with factor VIII-related antigen and CD31 i n 5 mu m sections from the paraffin blocks of tissue defined rumor ang iogenesis. Results: Follow-up was 95.1% complete, mean 5.2 +/- 3.0 yea rs, Lung cancer-related mortality rate was 24.4% at 5 years, Mean micr ovessel counts were 20.7 +/- 11.2 for FVIII and 29.6 +/- 18.1 for CD31 . Univariate analysis revealed an FVIII count of at least 20 (p = 0.02 5) and blood vessel invasion (p = 0.017) to be significant predictors of disease-related death, After adjustment for other patient and tumor characteristics, multivariate Cox regression analysis found an FVIII count of at least 20 (hazard ratio 2.9) and blood vessel invasion (haz ard ratio 3.7) to be significant independent correlates of lung cancer death (p = 0.018 and p = 0.011, respectively), CD31 quantitation did not predict survival on univariate or multivariate analyses and did no t correlate strongly with FVIII quantitation (Spearman's rank correlat ion r = 0.19), Conclusions: This analysis reveals a significant associ ation between tumor neovascularization and cancer-related mortality ra te among patients with stage I non-small-cell lung cancer. Microvessel quantitation of FVIII, as an indicator of tumor angiogenesis and meta static potential, may define a subset of patients with stage I non-sma ll-cell lung cancer who could benefit from adjuvant therapy after surg ical resection.