Expression of cell cycle regulatory proteins in breast carcinomas before and after preoperative chemotherapy
Expression of cell cycle regulatory proteins in breast carcinomas before and after preoperative chemotherapy
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DOI：
10.1023/a:1022165715043
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发表时间：
2003-03-01
影响因子：
3.8
通讯作者：
Filipits, M
中科院分区：
文献类型：
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作者：
Pohl, G;Rudas, M;Filipits, M
预测术前化疗反应的分子标志物在乳腺癌中具有重要的临床意义。因此，我们研究了乳腺癌患者术前化疗中细胞周期调控蛋白的表达与临床结局的关系。应用免疫组化方法检测乳腺癌术前化疗前后p21（Waf 1）、p27（Kip 1）、p53、cyclin D3和Ki-67的表达。将表达数据与临床参数和对环磷酰胺/甲氨蝶呤/5-氟尿嘧啶（CMF，n = 29）或表阿霉素/多西他赛（艾德，n = 36）术前化疗的反应进行比较。在术前化疗前后配对标本中，化疗后标本中p21（Waf 1）、p27（Kip 1）、p53和cyclin D3阳性细胞核的百分比显著高于化疗前标本，而Ki-67表达无明显变化。Ki-67高表达（p = 0.02）、雌激素受体阴性（p = 0.01）和孕激素受体阴性（p = 0.04）与化疗的完全病理反应相关，而其他标志物不能预测反应。总之，乳腺癌术前化疗后p21（Waf 1），p27（Kip 1），p53和cyclin D3的表达水平显着增加，但只有高Ki-67表达，阴性雌激素受体状态和阴性孕激素受体状态与术前化疗的完全病理反应。
Molecular markers predicting response to preoperative chemotherapy would be of major clinical relevance in breast cancer. Therefore, we studied the relationship between the expression of cell cycle regulatory proteins and clinical outcome in breast cancer patients receiving preoperative chemotherapy. Expression of p21(Waf1), p27(Kip1), p53, cyclin D3 and Ki-67 was determined in breast carcinomas by means of immunohistochemistry both prior and after preoperative chemotherapy. Expression data were compared with both clinical parameters and response to preoperative chemotherapy with either cyclophosphamide/methotrexate/5-fluorouracil (CMF, n = 29) or epirubicin/docetaxel (ED, n = 36). In paired samples before and after preoperative chemotherapy, the percentage of p21(Waf1), p27(Kip1), p53 and cyclin D3 positive nuclei of tumor cells in postchemotherapy specimens was significantly higher than the percentage in prechemotherapy samples but no change in Ki-67 expression was observed. High Ki-67 expression (p = 0.02), negative estrogen receptor status (p = 0.01) and negative progesterone receptor status (p = 0.04) were associated with complete pathologic response to chemotherapy, whereas the other markers did not predict response. In conclusion, expression levels of p21(Waf1), p27(Kip1), p53 and cyclin D3 significantly increased after preoperative chemotherapy in breast carcinomas but only high Ki-67 expression, negative estrogen receptor status and negative progesterone receptor status were associated with complete pathologic response to preoperative chemotherapy.