Köstler Wolfgang J, Brodowicz Thomas, Hudelist Gernot, Rudas Margaretha, Horvat Reinhard, Steger Günther G, Singer Christian F, Attems Johannes, Rabitsch Werner, Fakhrai Negar, Elandt Katarzyna, Wiltschke Christoph, Hejna Michael, Zielinski Christoph C
Clinical Division of Oncology, Department of Medicine I, Medical University of Vienna, 18-20 Waehringer Guertel, 1090, Vienna, Austria.
J Cancer Res Clin Oncol. 2005 Jul;131(7):420-8. doi: 10.1007/s00432-005-0670-3. Epub 2005 Apr 29.
Her-2/neu and p53-mediated signalling have been shown to interact at various cellular levels. However, the clinical relevance of p53 alterations in patients receiving trastuzumab for Her-2/neu-overexpressing metastatic breast cancer (MBC) remains unknown. The present study was performed to corroborate previous in vitro findings from our laboratory showing that trastuzumab induces growth arrest and apoptosis in a p53-independent manner.
Retrospective immunohistochemical (IHC) analysis for p53 protein expression was carried out on tumour specimens from 104 patients receiving trastuzumab-based treatment for Her-2/neu-overexpressing MBC at a single institution. p53 status was correlated with response (R) and clinical benefit (CB), median progression-free survival (PFS) time and overall survival (OAS) time in univariate and multivariate analyses.
Characteristics were similar between p53-negative and p53-positive tumours (all P>0.05). In univariate analyses, R (39% vs 26%, P=0.208), CB (70% vs 57%, P=0.218), PFS (6.2 months vs 4.2 months, P=0.186) and OAS (23.8 months vs 23.2 months, P=0.650) were similar for p53-positive tumours and p53-negative tumours, respectively. In multivariate analyses, p53 status was not a significant predictor of R, CB, PFS or OAS (all P>0.05).
p53 status, as determined by IHC, is not a predictor of the clinical efficacy of trastuzumab-based treatment in patients with Her-2/neu-overexpressing MBC.
已证实在多个细胞水平上，Her-2/neu和p53介导的信号传导存在相互作用。然而，对于接受曲妥珠单抗治疗的Her-2/neu过表达转移性乳腺癌（MBC）患者，p53改变的临床相关性仍不清楚。本研究旨在证实我们实验室先前的体外研究结果，即曲妥珠单抗以p53非依赖的方式诱导生长停滞和凋亡。
对一家机构中104例接受基于曲妥珠单抗治疗的Her-2/neu过表达MBC患者的肿瘤标本进行p53蛋白表达的回顾性免疫组织化学（IHC）分析。在单因素和多因素分析中，将p53状态与缓解率（R）、临床获益（CB）、中位无进展生存期（PFS）和总生存期（OAS）进行相关性分析。
p53阴性和p53阳性肿瘤的特征相似（所有P>0.05）。在单因素分析中，p53阳性肿瘤和p53阴性肿瘤的R（39%对26%，P=0.208）、CB（70%对57%，P=0.218）、PFS（6.2个月对4.2个月，P=0.186）和OAS（23.8个月对23.2个月，P=0.650）分别相似。在多因素分析中，p53状态不是R、CB、PFS或OAS的显著预测因素（所有P>0.05）。
通过IHC确定的p53状态，不是Her-2/neu过表达MBC患者基于曲妥珠单抗治疗临床疗效的预测指标。
