Davidoff A M, Herndon J E, Glover N S, Kerns B J, Pence J C, Iglehart J D, Marks J R
Department of Surgery, Duke University Medical Center, Durham, NC 27710.
Surgery. 1991 Aug;110(2):259-64.
The nuclear phosphoprotein p53 is expressed in all normal cells and appears to function in cell cycle regulation. Abnormally high levels of the protein are found in many different types of cancer. In breast carcinoma overexpression of p53 is associated with point mutations within highly conserved regions of the p53 gene. These altered genes encode stable p53 proteins that can be detected by standard immunohistochemical techniques unable to detect rapidly degraded wild-type protein. The level of p53 expression in 184 primary breast cancer specimens was assessed by immunohistochemical analysis and related to the following established prognostic factors for breast cancer: age, stage, metastatic involvement, concentration of estrogen and progesterone receptors, proliferative index, and HER-2/neu overexpression. Fifty (27%) of these primary breast cancer specimens had widespread overexpression of p53. Highly significant associations were found between p53 overexpression and late stage, metastatic spread, and low concentration of progesterone receptors. The presence of elevated levels of mutant p53 may itself be a prognostic factor in human breast cancer and activation of this oncogene may be important in the ability of a tumor to metastasize.
核磷蛋白p53在所有正常细胞中均有表达,似乎在细胞周期调控中发挥作用。在许多不同类型的癌症中都发现该蛋白水平异常升高。在乳腺癌中,p53的过表达与p53基因高度保守区域内的点突变有关。这些改变的基因编码稳定的p53蛋白,可通过标准免疫组织化学技术检测到,而该技术无法检测快速降解的野生型蛋白。通过免疫组织化学分析评估了184例原发性乳腺癌标本中p53的表达水平,并将其与以下已确定的乳腺癌预后因素相关联:年龄、分期、转移情况、雌激素和孕激素受体浓度、增殖指数以及HER-2/neu过表达。这些原发性乳腺癌标本中有50例(27%)存在广泛的p53过表达。在p53过表达与晚期、转移扩散以及低浓度孕激素受体之间发现了高度显著的关联。突变型p53水平升高本身可能是人类乳腺癌的一个预后因素,并且该癌基因的激活可能在肿瘤转移能力方面起重要作用。