A biologic risk model for stage I lung cancer: Immunohistochemical analysis of 408 patients with the use of ten molecular markers
A biologic risk model for stage I lung cancer: Immunohistochemical analysis of 408 patients with the use of ten molecular markers
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DOI：
10.1016/s0022-5223(99)70294-1
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发表时间：
1999-04-01
影响因子：
6
通讯作者：
Harpole, DH
中科院分区：
文献类型：
--
作者：
D'Amico, TA;Massey, M;Harpole, DH
目的：I期非小细胞肺癌患者的标准治疗是原发肿瘤切除；但复发率为28% ~ 45%。本研究评估了大量I期非小细胞肺癌患者中的一组分子标记物，以确定每个标记物的预后价值并创建生物学风险模型。方法：收集408例I期非小细胞肺癌患者的病理标本，随访至少5年，根据不同的致瘤机制，选择10个分子标记进行原发肿瘤的免疫组织化学分析。局部肿瘤扩张需要生长调节蛋白（表皮生长因子受体，原癌基因erbb -b2）；凋亡蛋白（p53, bcl-2）；和细胞周期调节蛋白（视网膜母细胞瘤隐性癌基因，KI-67），肿瘤局部侵袭需要血管生成（因子viii），远处转移的发展涉及粘附蛋白的表达（CD-44，唾液素- tn，血型A）。采用Cox比例风险回归分析构建癌症复发与死亡的独立风险模型。结果：多变量分析显示，以下分子标记物的风险显著升高：p53（风险比，1.68;P = 0.004）；因子viii（风险比，1.47;P = 0.033）；erbb -b2（风险比1.43;P = 0.044）；CD-44（风险比1.40;P = 0.050）；结论：细胞凋亡（p53）、血管生成（因子viii）、生长调节（erbb -b2）、粘附（CD-44）和细胞周期调节（视网膜母细胞瘤隐性癌基因）这5个分子标志物与复发和死亡风险相关，它们代表了独立的转移途径，本研究证实了该分子生物学风险模型在I期非小细胞肺癌患者中的有效性。
Objective: The standard treatment of patients with stage I non-small cell lung cancer is resection of the primary tumor; however, the recurrence rate is 28% to 45%. This study evaluates a panel of molecular markers in a large population of patients with stage I non-small cell lung cancer to determine the prognostic value of each marker and to create a biologic risk model. Methods: Pathologic specimens were collected From 408 consecutive patients after complete resection for stage I non-small cell lung cancer at a single institution, with follow-up of at least 5 years, A panel of 10 molecular markers was chosen for immunohistochemical analysis of the primary tumor on the basis of differing oncogenic mechanisms. Local tumor expansion requires growth regulating proteins (epidermal growth factor receptor, the protooncogene erb-b2); apoptosis proteins (p53, bcl-2); and cell cycle regulating proteins (retinoblastoma recessive oncogene, KI-67), Local tumor invasion requires angiogenesis (factor viii), The development of distant metastases involves the expression of adhesion proteins (CD-44, sialyl-Tn, blood group A). Cox proportional hazards regression analysis was used to construct an independent risk model for cancer recurrence and death. Results: Multivariable analysis demonstrated significantly elevated risk for the following molecular markers: p53 (hazard ratio, 1.68; P = .004); factor viii (hazard ratio, 1.47; P = .033); erb-b2 (hazard ratio, 1.43; P = .044); CD-44 (hazard ratio, 1.40; P = .050); and retinoblastoma recessive oncogene (hazard ratio, 0.747; P = .084), Conclusions: Five molecular markers were associated with the risk of recurrence and death, representing independent metastatic pathways: apoptosis (p53), angiogenesis (factor viii), growth regulation (erb-b2), adhesion (CD-44), and cell cycle regulation (retinoblastoma recessive oncogene), This study demonstrates the validity of this molecular biologic risk model in patients with stage I nonsmall cell lung cancer.