Macchiarini P, Fontanini G, Dulmet E, de Montpreville V, Chapelier A R, Cerrina J, Ladurie F L, Dartevelle P G
Department of Thoracic and Vascular Surgery, Hopital Marie-Lannelongue, Paris-Sud University, Plessis Robinson, France.
Ann Thorac Surg. 1994 Jun;57(6):1534-9. doi: 10.1016/0003-4975(94)90117-1.
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.
我们试图找出累及胸廓入口的切除非小细胞肺癌局部侵袭性强及治疗失败晚的生物学依据。对28例行新的经颈入路手术患者的肿瘤标本进行分析，检测肿瘤增殖活性、抑癌基因p53、肿瘤细胞对瘤内及瘤周血管的侵袭、血管生成情况（新毛细血管和小静脉的诱导）以及其他生物学变量。89%的肿瘤为中分化或低分化，89%表现为中等或高增殖活性，39%显示p53异常，71%有血管生成诱导，39%的肿瘤血管侵袭呈阳性。中位随访时间为3.5年（范围8至超过145个月），总体预计5年生存率为29%，中位无病间期为23个月。生存及无病间期的单因素和多因素分析结果显示，血管生成程度（密度小于1与大于1，新生血管数量小于6与大于6）是无病间期唯一独立且显著的预测因素。肿瘤血管生成密度为1或更高且新生血管数量为6或更多的患者，其原发肿瘤发生全身复发的相对风险显著高于低风险患者（p = 0.0001）。结果表明，血管生成与治疗失败晚期（转移）显著相关，且这在血管的关键密度和数量时出现。
