原发性乳腺癌P-糖蛋白表达与化疗预后的关系

Over expression of P glycoprotein in primary breastcancer as a predictor of postoperative survival

目的：探索临床上乳腺癌化疗失败是否与多药耐受表型Ｐ糖蛋白（Ｐｇｐ）有关。方法：使用抗Ｐｇｐ的单克隆抗体的免疫组织化学方法（ＳＰ方法）和微波加热抗原修复技术检测５６例乳腺癌患者组织切片Ｐｇｐ表达状况。结果：（１）术前未接受任何化学治疗的乳腺癌Ｐｇｐ表达的阳性率为７６８％（４３／５６），并且Ｐｇｐ表达程度与提示乳腺癌疾病进展和预后的各项临床病理参数，如年龄、原发灶大小、淋巴结转移数、ＴＮＭ分期、病理学类型和组织学分级无显著相关性（Ｐ＞００５）；（２）Ｐｇｐ阴性组的总体生存率及各时点生存率明显高于阳性组（Ｐ＜００１），经ＣＯＸ多元回归分析模型调整各因素的作用后，Ｐｇｐ对生存率的影响仍然是显著的（Ｐ＜０２，检验水平α＝０．２）。结论：（１）Ｐｇｐ存在于化疗药物作用以前的原发性乳腺癌中，药物耐受是先天性的。（２）Ｐｇｐ在预测药物耐受。

Objective: The differences of P glycoprotein (P gp) expression were explored to clarify its association with MDR in breast cancer. Methods: This study examines P gp expression of formalin fixed. Paraffin embedded tumor samples from 56 patients with primary breast cancer, staged in TNMⅡ or Ⅲ, who had not received any chemotherapy before surgery. All patients under this study were treated with systemic postoperative adjuvant chemotherapy and followed up from the first day after surgery to the beginning of this study.Immunohistochemistry was performed by the streptavidin peroxidase conjugated method using a monoclonal antibody specifically against P gp.Results:P gp immunoreactivity was present in 43(76.8%) cases of the 56 patients,in a heterogeneous cytoplasmic or predominantly membranous staining fashion,and P gp immunoreactivity was not associated with any of the clinicopatholgical parameters such as age,tumor size,axillary lymph node metastasis,clinical TNM stage,histologic type and tumor grade(P>0.05,respectively),suggesting intrinstic drug resistance of human breast cancer.Our data show also that the P gp expression positive group were worse than the negative's in overall survival duration after adjustment by multivariate analysis(COX's model)for other prognostic factors(P<0 2).Conclusion: P gp is a useful marker of poor prognosis in patients with primary breast cancer undergoing chemotherapy.