Pellikainen M J, Pekola T T, Ropponen K M, Kataja V V, Kellokoski J K, Eskelinen M J, Kosma V-M
Department of Pathology and Forensic Medicine, University of Kuopio, FIN-70211 Kuopio, Finland.
J Clin Pathol. 2003 Mar;56(3):214-20. doi: 10.1136/jcp.56.3.214.
To evaluate the expression and prognostic relevance of p21(WAF1) in breast cancer and to investigate its association with p53, activator protein 2 (AP-2), and cell proliferation (as assessed by Ki-67 expression).
p21(WAF1) expression was analysed immunohistochemically in a large prospective, consecutive series of 420 patients with breast cancer diagnosed and treated between 1990 and 1995 at Kuopio University Hospital, Kuopio, Finland. Inter-relations between p21(WAF1) expression and p53, AP-2, and Ki-67 were evaluated. The expression of p21(WAF1) was also compared with clinicopathological parameters and the patients' survival.
In general, nuclear p21(WAF1) expression was low in carcinomas (median, 2.5%; range, 0-70%). Expression was lowest in lobular carcinomas (chi(2) = 7.4; p = 0.025). p21(WAF1) positive tumours were more often p53 positive (chi(2) = 4.2; p = 0.041) but expression of p21(WAF1) did not correlate with AP-2 expression or Ki-67 in the whole patient group. In addition, the combined expression of p21 and p53 was not associated with AP-2 expression. High nuclear p21(WAF1) positivity (n = 160; 38%) was associated with poor differentiation (chi(2) = 8.1; p = 0.017). In the univariate analyses, p21(WAF1) expression had no prognostic value for predicting breast cancer related survival (BCRS) or recurrence free survival (RFS) in the whole patient group or in the subgroups investigated. However, in postmenopausal patients with lymph node metastases, and oestrogen receptor (ER) and/or progesterone receptor (PR) positive tumours, high p21(WAF1) expression predicted response to adjuvant hormonal treatment with antioestrogens. In the univariate analysis, the significant factors for predicting BCRS were Ki-67 expression, stage, lymph node status, histological grade, ER and PR status, and those for RFS were Ki-67 expression, stage, and lymph node status. In the multivariate analysis, the independent predictors of shorter BCRS were high cell proliferation activity measured by Ki-67 expression (p < 0.001), advanced stage (p < 0.001), and poor differentiation (p = 0.048). Shorter RFS was independently predicted by high cell proliferative activity (p < 0.001) and advanced stage (p < 0.001).
The regulation of p21(WAF1) seems to occur independently of p53 or AP-2 and analysing p21(WAF1) expression provided no prognostic information for patients with breast cancer.
评估p21（WAF1）在乳腺癌中的表达及其与预后的相关性，并研究其与p53、激活蛋白2（AP - 2）以及细胞增殖（通过Ki - 67表达评估）之间的关联。
采用免疫组织化学方法分析了1990年至1995年间在芬兰库奥皮奥大学医院诊断和治疗的420例乳腺癌患者的大样本前瞻性连续队列中p21（WAF1）的表达情况。评估了p21（WAF1）表达与p53、AP - 2和Ki - 67之间的相互关系。还将p21（WAF1）的表达与临床病理参数及患者生存率进行了比较。
总体而言，癌组织中核p21（WAF1）表达较低（中位数为2.5%；范围为0 - 70%）。小叶癌中的表达最低（χ² = 7.4；p = 0.025）。p21（WAF1）阳性肿瘤更常为p53阳性（χ² = 4.2；p = 0.041），但在整个患者组中p21（WAF1）的表达与AP - 2表达或Ki - 67无关。此外，p21和p53的联合表达与AP - 2表达无关。高核p21（WAF1）阳性（n = 160；38%）与低分化相关（χ² = 8.1；p = 0.017）。在单因素分析中，p21（WAF1）表达对整个患者组或所研究的亚组中预测乳腺癌相关生存（BCRS）或无复发生存（RFS）没有预后价值。然而，在绝经后有淋巴结转移且雌激素受体（ER）和/或孕激素受体（PR）阳性肿瘤的患者中，高p21（WAF1）表达预示对抗雌激素辅助激素治疗有反应。在单因素分析中，预测BCRS的显著因素是Ki - 67表达、分期、淋巴结状态、组织学分级、ER和PR状态，而预测RFS的因素是Ki - 67表达、分期和淋巴结状态。在多因素分析中，Ki - 67表达所测量的高细胞增殖活性（p < 0.001）、晚期（p < 0.001）和低分化（p = 0.048）是BCRS较短的独立预测因素。高细胞增殖活性（p < 0.001）和晚期（p < 0.001）是RFS较短的独立预测因素。
p21（WAF1）的调节似乎独立于p53或AP - 2发生，分析p21（WAF1）表达对乳腺癌患者没有提供预后信息。
