Harpole D H, Marks J R, Richards W G, Herndon J E, Sugarbaker D J
Lung Cancer Research Laboratory, Division of Thoracic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Clin Cancer Res. 1995 Jun;1(6):659-64.
Historical information and pathological material from 150 consecutive patients with localized adenocarcinoma of the lung was collected to evaluate oncogene expression of erbB-2 and p53, and erbB-2 gene amplification. Pathological material after resection was reviewed to verify histological staging, and patient follow-up was complete in all cases for at least 68 months. Immunohistochemistry of erbB-2 (HER-2/neu) and p53 oncogene expression was performed on two separate paraffin tumor blocks for each patient with normal lung as control. Gene amplification of erbB-2 was measured after DNA extraction from 20-micrometer sections of erbB-2-positive and -negative tumors. All analyses were blinded and included Kaplan-Meier survival estimates with Cox proportional hazards regression modeling. Two adequate blocks of tumor and normal lung were available for 138 (92%) patients. Immunohistochemical identification of expression of p53 was observed in 49 (37%) patients and erbB-2 in 17 (13%) patients. DNA dot blot analyses were performed on 17 erbB-2-positive and 13 randomly selected erbB-2-negative tumors. There was 1 (6%) of 17 erbB-2-positve tumors with 4-fold erbB-2 gene amplification. Actual 5-year survival was 63% and actuarial 10-year survival was 59% for the entire population of 150 patients. Significant univariate predictors (P < 0.05) of cancer death were the presence of symptoms, tumor size >3 cm, poor differentiation, visceral pleural invasion, and p53 expression. Multivariate analysis associated symptoms and p53 expression as independent factors with decreased survival. Thus, this project examined p53 and erbB-2 expression in patients with localized adenocarcinoma and associated p53 status with survival. Multicenter collection of data should allow the development of a model of cancer recurrence in this most common lung cancer.
收集了150例连续性局部肺腺癌患者的历史信息和病理材料,以评估erbB-2和p53的癌基因表达以及erbB-2基因扩增情况。对切除后的病理材料进行复查以核实组织学分期,所有病例的患者随访均完整,时间至少为68个月。对每位患者的两个单独石蜡肿瘤块进行erbB-2(HER-2/neu)和p53癌基因表达的免疫组织化学检测,以正常肺组织作为对照。从erbB-2阳性和阴性肿瘤的20微米切片中提取DNA后,测量erbB-2的基因扩增情况。所有分析均采用盲法,包括Kaplan-Meier生存估计和Cox比例风险回归模型。138例(92%)患者可获得两块足够的肿瘤和正常肺组织块。49例(37%)患者观察到p53表达的免疫组织化学鉴定结果,17例(13%)患者观察到erbB-2表达的免疫组织化学鉴定结果。对17例erbB-2阳性肿瘤和13例随机选择的erbB-2阴性肿瘤进行DNA斑点印迹分析。17例erbB-2阳性肿瘤中有1例(6%)出现4倍erbB-2基因扩增。150例患者总体的实际5年生存率为63%,精算10年生存率为59%。癌症死亡的显著单因素预测指标(P<0.05)包括症状的存在、肿瘤大小>3cm、低分化、脏层胸膜侵犯和p53表达。多因素分析将症状和p53表达作为与生存率降低相关的独立因素。因此,本项目研究了局部肺腺癌患者的p53和erbB-2表达,并将p53状态与生存率相关联。多中心数据收集应有助于建立这种最常见肺癌的癌症复发模型。