Angiogenesis: an indicator of metastasis in non-small cell lung cancer invading the thoracic inlet.
We have attempted to identify a biologic rationale for the local aggressiveness and late treatment failure of resected non-small cell lung cancer involving the thoracic inlet. Tumor specimens from 28 patients who underwent a new transcervical approach were analyzed for the expression of tumor proliferative activity, suppressor-gene p53, intratumoral and peritumoral blood vessel invasion by tumor cells, the presence and degree of angiogenesis (induction of new capillaries and venules), and other biologic variables. Eighty-nine percent of the neoplasms were moderately or poorly differentiated, 89% expressed either an intermediate or high proliferative activity, 39% showed p53 aberrations, 71% exhibited induction of angiogenesis, and 39% had tumors that were positive for blood vessel invasion. With a median follow-up time of 3.5 years (range, 8 to 145+ months), the overall projected 5-year survival was 29% and the median disease-free interval was 23 months. Results of univariate and multivariate analysis of survival and the disease-free interval identified the degree of angiogenesis (density less than 1 versus more than 1 and number of neovessels less than 6 versus more than 6) as the only independent and significant predictors of the disease-free interval. Patients whose tumor showed a density of angiogenesis of 1 or greater and a number of neovessels of 6 or greater faced a significantly (p = 0.0001) higher relative risk of suffering systemic recurrence of their primary tumor than did their low-risk counterparts. Results demonstrate that angiogenesis significantly correlates with late treatment failure (metastasis), and this is acquired at a critical density and number of vessels.
Macchiarini
P
P
Department of Thoracic and Vascular Surgery, Hopital Marie-Lannelongue, Paris-Sud University, Plessis Robinson, France.
Fontanini
G
G
Dulmet
E
E
de Montpreville
V
V
Chapelier
A R
AR
Cerrina
J
J
Ladurie
F L
FL
Dartevelle
P G
PG
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology / Q000556:secondary; D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology* / Q000556:secondary*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology / Q000556:secondary; D002453:Cell Cycle; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008938:Mitosis; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000235:genetics; D015996:Survival Rate; D013899:Thoracic Neoplasms / Q000235:genetics / Q000473:pathology* / Q000556:secondary*