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J Thorac Cardiovasc Surg 1998;115:652-659
© 1998 Mosby, Inc.

GENERAL THORACIC SURGERY

Angiogenesis As A Predictor Of Survival After Surgical Resection For Stage I Non-Small-Cell Lung Cancer

From the Division of Cardiothoracic Surgery, Department of Surgery^a and Department of Pathology and Laboratory Medicine,^b Emory University School of Medicine, Atlanta, Ga.

Read at the Seventy-seventh Annual Meeting of The American Association for Thoracic Surgery, Washington, D.C., May 4-7, 1997.

Received for publication May 7, 1997; revisions requested July 15, 1997; revisions received Nov. 11, 1997; accepted for publication Nov. 11, 1997. Address for reprints: Joseph I. Miller, MD, 25 Prescott St., NE, Suite 3420, Atlanta, GA 30308.

Objectives: Some patients with surgically resected stage I non-small-cell lung cancer eventually have metastatic disease. A histologic marker of metastatic potential and diminished survival for stage I non-small-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 with stage I non-small-cell lung cancer from 1985 through 1990. Visual quantitation of microvessels immunostained with factor VIII–related antigen and CD31 in 5 µm sections from the paraffin blocks of tissue defined rumor angiogenesis.
Results: Follow-up was 95.1% complete, mean 5.2 ± 3.0 years. Lung cancer-related mortality rate was 24.4% at 5 years. Mean microvessel 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 = 0.025) 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 (hazard 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 not correlate strongly with FVIII quantitation (Spearman's rank correlation r = 0.19).
Conclusions: This analysis reveals a significant association between tumor neovascularization and cancer-related mortality rate among patients with stage I non-small-cell lung cancer. Microvessel quantitation of FVIII, as an indicator of tumor angiogenesis and metastatic potential, may define a subset of patients with stage I non-small-cell lung cancer who could benefit from adjuvant therapy after surgical resection.

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