Eid H, Van der Looij M, Institoris E, Géczi L, Bodrogi I, Oláh E, Bak M
Department of Cytopathology, National Institute of Oncology, Budapest, Hungary.
Anticancer Res. 1997 Jul-Aug;17(4A):2663-9.
Several prior studies revealed positive p53 expression via immunohistochemistry (IHC) in a large percentage of germ cell testicular cancers (GCTTs). However, the predicting and prognostic value of this protein remains to be defined. Therefore, the aim of our study was to further clarify the role of p53 protein in GCTTs and to look for correlations between its gene expression and other disease parameters, including histological subtype, stage and clinical resistance sensitivity. Furthermore, we correlated p53 protein expression with that of MDRI gene product protein (Pgp) in order to examine the interrelationship between these two markers.
77 untreated patients with GCTTs were investigated for their p53 expression using monoclonal antibody and immunohistochemistry in paraffin-embedded specimens. There were 34 patients with stage I, 16 with stage II, 27 with stage III disease.
All tumor types, except differentiated teratomas, were immunoreactive for p53 to a various extent ranging from scarcely positive to homogeneously stained tumor cells. Seminomas (S) and embryonal carcinoma (EC) components showed the most positive nuclear staining. p53 expression showed a significant inverse correlation with the stage of disease (P < 0.0003). There was a significant positive relationship between p53 immunoreactivity and response to treatment (P = 0.0012), i.e. high levels of p53 expression correlated with clinical sensitivity of the tumors to chemotherapy. We could demonstrate a statistically significant opposite relationship between p53 and Pgp immunoreactivity (P < 0.0005).
Our results show that p53 status in tumor cells may be a strong determinate of susceptibility to chemotherapy and that p53 overexpression has a favorable prognosis in terms of response to treatment in GCTTs. Moreover, the findings provide clinical evidence for the presense of significant relationship between p53 and MDR1/Pgp immunoreactivity. They also suggest that patients resistant to chemotherapy and lacking p53 expression might benefit from an alternative appropriately designed chemotherapeutic regimen to achieve further successful treatment in GCTTs.
此前的多项研究通过免疫组织化学（IHC）揭示，在大部分睾丸生殖细胞癌（GCTT）中p53表达呈阳性。然而，这种蛋白的预测和预后价值仍有待确定。因此，我们研究的目的是进一步阐明p53蛋白在GCTT中的作用，并寻找其基因表达与其他疾病参数之间的相关性，包括组织学亚型、分期和临床耐药敏感性。此外，我们将p53蛋白表达与多药耐药基因1（MDR1）基因产物蛋白（Pgp）的表达进行关联，以研究这两种标志物之间的相互关系。
使用单克隆抗体和免疫组织化学方法，对77例未经治疗的GCTT患者石蜡包埋标本中的p53表达进行研究。其中I期患者34例，II期患者16例，III期患者27例。
除分化型畸胎瘤外，所有肿瘤类型对p53均有不同程度的免疫反应，从弱阳性到肿瘤细胞均匀染色不等。精原细胞瘤（S）和胚胎癌（EC）成分显示出最强的核染色阳性。p53表达与疾病分期呈显著负相关（P < 0.0003）。p53免疫反应性与治疗反应之间存在显著正相关（P = 0.0012），即p53高表达与肿瘤对化疗的临床敏感性相关。我们能够证明p53和Pgp免疫反应性之间存在统计学上的显著反向关系（P < 0.0005）。
我们的结果表明，肿瘤细胞中的p53状态可能是化疗敏感性的一个重要决定因素，并且在GCTT中，p53过表达在治疗反应方面具有良好的预后。此外，这些发现为p53与MDR1/Pgp免疫反应性之间存在显著关系提供了临床证据。它们还表明，对化疗耐药且缺乏p53表达的患者可能受益于另一种经过适当设计的化疗方案，以在GCTT中实现进一步的成功治疗。
