天津医药

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P53在三阴性乳腺癌中的表达及其与铂类化疗药物敏感性的关系

尼杰,智英辉,只向成   

  1. 天津医科大学附属肿瘤医院乳腺三科
  • 收稿日期:2012-06-21 修回日期:2012-10-08 出版日期:2013-04-15 发布日期:2013-04-15
  • 通讯作者: 只向成

NI Jie ,ZHI Ying hui,ZHI Xiang cheng   

  1. Department of Breast Cancer, Tianjin Medical University, Cancer Institute and Hospital, Tianjin 300060, China
  • Received:2012-06-21 Revised:2012-10-08 Published:2013-04-15 Online:2013-04-15
  • Contact: ZHI Xiang cheng

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摘要：

【摘要】目的 探讨P53对三阴性乳腺癌（TNBC）预后的意义及其与铂类化疗药物敏感性的关系。方法选取 291例原发性乳腺癌患者的新鲜癌组织（新发组），采用肿瘤原代细胞胶原凝胶体包埋化疗药物敏感性检测技术（CD-DST法）进行常用化疗药物（多西他赛、表柔比星、吡柔比星、诺维本、顺铂）的体外检测，用免疫组化方法检测患者中P53的表达，分析其与各临床病理特征及化疗药物敏感性的关系。同时回顾性收集有完整临床和随访资料及完整的生物学指标检测结果的153例TNBC患者资料作为随访组，采用Cox回归分析影响患者无瘤生存期的因素。结果 291例原发性乳腺癌患者中，TNBC患者43例，其中P53阳性表达率为62.79%（27/43），高于非三阴性乳腺癌（30.65%，76/248）。在组织学Ⅲ级患者中，P53的阳性表达率为66.04%，高于组织学Ⅰ级（23.73%)和Ⅱ级（30.17%）的阳性表达率。P53是影响TNBC患者无瘤生存期的影响因素，其阳性表达者的5年无瘤生存率低于阴性者（69.7% vs 89.4%，P = 0.001）。对顺铂化疗药物敏感的TNBC中P53阳性表达率低于耐药组，差异有统计学意义（P = 0.018）。结论 P53阳性是判断TNBC预后较差的指标之一，其表达和铂类化疗药物敏感性呈负相关。

关键词: 乳腺肿瘤, 肿瘤抑制蛋白质p53, 铂化合物, 预后, 存活率分析, 化疗药物敏感性

Abstract: [Abstract] Objective  To investigate the relationship between the expression of P53 and the prognosis and plati? num-based chemosensitivity in triple negative breast cancer (TNBC). Methods  A total of 291 fresh breast cancer samples were collected . The collagen gel droplet embedded culture drug sensitivity tests (DC-DST) were used to measure the different chemosensitivities of usual chemotheray drugs including docetaxel, epirubicin, pirarubicin navelbine and cisplatin in cultured primary cells in vitro. The expression of P53 was tested by immunohistochemistry. The relationship between P53 expression and clinicopathological characteristics and prognosis was analyzed. The full clinical and follow-up data and biological indicator results in 153 patients with TNBC were retrospectively collected.The Cox regression analysis was used to detect the factors affecting tumor-free survival in patients. Results  There were 43 TNBC patients in 291 patients with primary breast cancer. There was a higher rate of P53 expression (62.79% ，27/43) in patients with TNBC than that of patients with non-TNBC (30.65%，76/248). The positive expression of P53 was higher in patients with grade Ⅲ breast cancer (66.04%) than that in patients with gradeⅠ(23.73%) and gradeⅡ(30.17%) breast cancer. The expression of P53 was an independent factor influencing tumor-free survival in patients with TNBC. There was a significantly lower 5-year tumor-free survival rate in patients with the positive expression of P53 than that of patients with negative expression of P53 (69.70% vs 89.40%, P= 0.001). The positive rate of P53 expression was significantly lower in patients with TNBC who were sensitive to cisplatin than that in patients with drug-resistance (P =0.018). Conclusion  The positive expression of P53 suggests a poor prognosis in TNBC patients. The expression of P53 is negatively correlated with the chemosensitivity of platinum-based chemotherapy.

Key words: breast neoplasms, tumor suppressor protein p53, platinum compounds, prognosis, survival analysis, chemosensitivity