Beck T, Weller E E, Weikel W, Brumm C, Wilkens C, Knapstein P G
Gynecological Clinic, University of Mainz, Germany.
Gynecol Oncol. 1995 Apr;57(1):96-104. doi: 10.1006/gyno.1995.1104.
Mutations of the p53 gene often result in the overexpression of p53 protein. Previous studies have suggested that the function of p53 and its mutant protein forms may be linked with the disease course of patients with a breast carcinoma. In the present study, we tested 462 primary breast carcinomas for the presence of p53 antigen using immunohistochemical methods employing antibodies against the clone, DO-1. These tumors were also immunohistochemically stained using the monoclonal antibody, MIB-1, in order to demonstrate the presence of Ki67. Comparison of the presence of p53 with other prognostic parameters revealed highly significant negative correlations with estrogen- and progesterone-receptor status (P < 0.001 and P = 0.001, respectively) as well as positive correlations with both the presence of MIB-1 (P < 0.001) and the histological grading (P = 0.008). The presence of p53 was not correlated with tumor stage and node status. Evaluation of the findings for all 462 tumors as well as for node-positive and -negative subgroups revealed less favorable findings for overall survival and the disease-free period for both p53-positive tumors (for total group, overall survival, P = 0.0002, disease-free period, P = 0.02; for node-positive group, overall survival, P = 0.0004, disease-free period, P = 0.1045) and breast carcinomas with higher proportions of cell nuclei positive for MIB-1 (total, overall survival, P = 0.0026, disease-free period, P = 0.0022; node-positive, overall survival, P = 0.021, disease-free period, P = 0.0882). We were able to demonstrate that p53 expression in breast carcinomas means a significantly worse prognosis for grade II tumors (overall survival, P = 0.0002; disease-free period, P = 0.0116), for overall survival in the case of estrogen-receptor-positive tumors (P = 0.014), and for tumors showing increased proliferation activity (overall survival, P = 0.0477).
p53基因的突变常常导致p53蛋白的过度表达。先前的研究表明，p53及其突变蛋白形式的功能可能与乳腺癌患者的病程有关。在本研究中，我们采用针对克隆体DO-1的抗体，运用免疫组织化学方法检测了462例原发性乳腺癌中p53抗原的存在情况。这些肿瘤还用单克隆抗体MIB-1进行了免疫组织化学染色，以显示Ki67的存在。p53的存在情况与其他预后参数的比较显示，其与雌激素和孕激素受体状态呈高度显著负相关（分别为P < 0.001和P = 0.001），与MIB-1的存在情况（P < 0.001）以及组织学分级（P = 0.008）呈正相关。p53的存在情况与肿瘤分期和淋巴结状态无关。对所有462例肿瘤以及淋巴结阳性和阴性亚组的结果评估显示，p53阳性肿瘤（对于总组，总生存期，P = 0.0002，无病生存期，P = 0.02；对于淋巴结阳性组，总生存期，P = 0.0004，无病生存期，P = 0.1045）以及MIB-1细胞核阳性比例较高的乳腺癌（总体，总生存期，P = 0.0026，无病生存期，P = 0.0022；淋巴结阳性，总生存期，P = 0.021，无病生存期，P = 0.0882）在总生存期和无病期方面的结果均较差。我们能够证明，乳腺癌中p53的表达对于II级肿瘤（总生存期，P = 0.0002；无病生存期，P = 0.0116）、雌激素受体阳性肿瘤的总生存期（P = 0.014）以及增殖活性增加的肿瘤（总生存期，P = 0.0477）意味着预后明显更差。
