Dellas A, Schultheiss E, Almendral A C, Gudat F, Oberholzer M, Feichter G, Moch H, Torhorst J
Department of Gynaecology, University of Basel, Switzerland.
Int J Cancer. 1997 Aug 22;74(4):421-5. doi: 10.1002/(sici)1097-0215(19970822)74:4<421::aid-ijc10>3.0.co;2-c.
Recent results suggest that p53 inactivation is required for cervical-carcinoma development. The mdm-2 oncogene, which forms an auto-regulatory feedback loop with the normal p53 protein, has been found amplified in human carcinomas, thus abolishing the anti-proliferative function of p53. To investigate whether the mdm-2/p53 interaction plays a role in cervical neoplasms, we performed an immunohistochemical study in archival fixed, embedded specimens that included 178 pre-cancerous lesions (CIN) and invasive squamous-cell carcinomas of clinical stage IB. In addition to p53, we assessed the p53-associated protein, mdm-2, and the Ki-67 labelling index (LI). The presence of HPV was assessed by in situ DNA hybridization. Tumor expression of all nuclear proteins was scored as fraction of positive CIN or cancer nuclei. The analysis demonstrated a significant association of the Ki-67 LI with grade of atypia in cervical neoplasms. p53 accumulation and mdm-2 expression are higher in invasive carcinomas than in pre-cancerous lesions. No correlation was observed with HPV status. An inverse correlation was found between increased tumor-cell proliferation and mdm-2 expression in invasive carcinomas (p < 0.0001). mdm-2 expression was significantly associated with p53 accumulation (p < 0.02). However, the investigated nuclear proteins were not associated with overall survival in patients with invasive carcinomas. Cox stepwise-regression analysis revealed regional lymph node status and depth of invasion to be independent parameters.
近期研究结果表明，p53失活是宫颈癌发生发展所必需的。mdm-2癌基因与正常p53蛋白形成一种自动调节反馈环，已发现在人类癌症中该基因呈扩增状态，从而消除了p53的抗增殖功能。为研究mdm-2/p53相互作用在宫颈肿瘤中是否发挥作用，我们对存档的固定、包埋标本进行了免疫组化研究，这些标本包括178例癌前病变（CIN）和临床分期为IB期的浸润性鳞状细胞癌。除了p53，我们还评估了与p53相关的蛋白mdm-2以及Ki-67标记指数（LI）。通过原位DNA杂交评估HPV的存在情况。所有核蛋白的肿瘤表达情况按CIN或癌细胞核阳性比例进行评分。分析表明，Ki-67 LI与宫颈肿瘤的异型程度显著相关。浸润性癌中的p53蓄积和mdm-2表达高于癌前病变。未观察到与HPV状态的相关性。在浸润性癌中发现肿瘤细胞增殖增加与mdm-2表达呈负相关（p < 0.0001）。mdm-2表达与p53蓄积显著相关（p < 0.02）。然而，所研究的核蛋白与浸润性癌患者的总生存期无关。Cox逐步回归分析显示区域淋巴结状态和浸润深度是独立参数。
