Visscher D W, Castellani R, Wykes S M, Sarkar F H, Hussain M E
Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan.
Breast Cancer Res Treat. 1993 Dec;28(3):261-6. doi: 10.1007/BF00666587.
Metastatic phenotype in human solid tumors is believed to follow stochastic acquisition of structural genetic aberrations-so-called multistep tumor progression. We tested this hypothesis in breast carcinoma by immunostaining 89 stage-heterogeneous cases for the products of three genes (p53, ERBB-2, and EGFR) which are frequently altered in this tumor system. Variable relationships were observed between advanced disease stage and immunostaining for individual gene products (ERBB-2 - p = 0.05, EGFR - p = 0.02, p53 - p = 0.12, Chi Square test). Regional or distant metastases at presentation correlated with multiple oncogene/tumor suppressor gene expression abnormalities: node negative -59% none positive, 29% one positive, 12% two or more positive, vs. node positive -37% none positive, 23% one positive, 39% two or more positive (p = 0.01). Only 2/12 (17%) of tumors with distant metastases at presentation were negative for abnormal expression of any of these gene products, and 7/12 (58%) were positive for two or three. Among axillary node negative patients who developed recurrences, 67% exhibited staining for at least one gene product, compared to only 27% of those without recurrences (p = 0.02). All 5 cases with abnormal staining for each gene product had regional or distant metastases at presentation and recurred. In multivariate analysis, individual expression of p53 outweighed expression of ERBB-2 and EGFR in correlation with outcome. These data suggest clinical neoplastic progression of breast carcinomas correlates with cumulative genetic events detectable by protein expression. Short term recurrence, however, may correlate more closely with abnormal expression of p53 than with EGFR or ERBB-2.
人类实体瘤中的转移表型被认为是结构遗传畸变随机获得的结果，即所谓的多步骤肿瘤进展。我们通过对89例不同分期的乳腺癌病例进行免疫染色，检测三个基因（p53、ERBB-2和EGFR）的产物，这三个基因在该肿瘤系统中经常发生改变，以此来验证这一假说。在疾病晚期与单个基因产物的免疫染色之间观察到了不同的关系（ERBB-2 - p = 0.05，EGFR - p = 0.02，p53 - p = 0.12，卡方检验）。就诊时的区域或远处转移与多种癌基因/肿瘤抑制基因表达异常相关：淋巴结阴性患者中，59%无阳性表达，29%有一个阳性表达，12%有两个或更多阳性表达；而淋巴结阳性患者中，37%无阳性表达，23%有一个阳性表达，39%有两个或更多阳性表达（p = 0.01）。就诊时伴有远处转移的肿瘤中，只有2/12（17%）的肿瘤这三种基因产物的异常表达均为阴性，7/12（58%）的肿瘤有两个或三个基因产物呈阳性。在出现复发的腋窝淋巴结阴性患者中，67%至少有一种基因产物染色阳性，而未复发患者中这一比例仅为27%（p = 0.02）。每种基因产物染色异常的所有5例患者就诊时均有区域或远处转移且均复发。在多变量分析中，p53的单独表达与预后的相关性超过了ERBB-2和EGFR的表达。这些数据表明，乳腺癌的临床肿瘤进展与通过蛋白质表达可检测到的累积遗传事件相关。然而，短期复发可能与p53的异常表达比与EGFR或ERBB-2的异常表达关系更为密切。
