三阴性乳腺癌EGFR、Ki-67、P53及CTC表达与预后的关系研究

Relationship between expression levels of EGFR,Ki-67,P53 and CTC and the prognosis of triple negative breast cancer

目的探讨三阴性乳腺癌表皮生长因子受体(EGFR)、细胞核增殖相关抗原Ki-67(Ki-67)、P53及循环肿瘤细胞(CTC)表达与预后的关系。方法选取95例三阴性乳腺癌患者,免疫组化检测病理组织标本中EGFR、Ki-67、P53表达;所有患者接受8个周期化疗,采用膜滤过分离肿瘤细胞技术(ISET)检测化疗前后的CTC表达,并分析化疗前后CTC表达与化疗疗效的关系;分析CTC与EGFR、Ki-67、P53表达的关联性;随访患者无进展生存期(PFS),采用COX回归分析三阴性乳腺癌进展的危险因素。结果EGFR、Ki-67、P53阳性检出率分别为44.21%(42/95)、63.16%(60/95)、56.84%(54/95);化疗后患者的CTC阳性检出率(14.74%)低于化疗前(61.05%,P<0.05);化疗疗效与化疗后CTC阳性表达呈负相关(P<0.001);COX回归分析显示,临床分期为Ⅲ期、EGFR阳性、化疗后CTC阳性是三阴性乳腺癌进展的独立危险因素(P<0.05);不同临床分期患者PFS比较,Ⅰ期>Ⅱ期>Ⅲ期,EGFR阳性患者PFS短于阴性患者,化疗后CTC阳性患者PFS短于阴性患者(P<0.05)。结论化疗前EGFR阳性表达、化疗后CTC阳性表达与三阴性乳腺癌患者预后差有关,化疗后CTC阳性率越低患者化疗疗效越好。

Objective To investigate the relationship between expression levels of epidermal growth factor receptor(EGFR),proliferation marker protein Ki-67(Ki-67),P53 and circulating tumor cell(CTC)and the prognosis of triple negative breast cancer.Methods A total of 95 patients with triple negative breast cancer were selected.The expression levels of EGFR,Ki-67 and P53 in pathological tissue specimens were detected by immunohistochemistry.All patients underwent 8 cycles of chemotherapy,and the expression of CTC was detected before and after chemotherapy by isolation epithelial tumor cells(ISET).The relationship between CTC expression before and after chemotherapy and efficacy of chemotherapy was analyzed.The correlation between CTC and expression levels of EGFR,Ki-67 and P53 was analyzed.Patients were followed up for progression free survival(PFS).Risk factors of progression for triple negative breast cancer were analyzed by COX regression.Results The positive detection rates of EGFR,Ki-67 and P53 were 44.21%(42/95),63.16%(60/95)and 56.84%(54/95).The positive detection rate of CTC was lower in patients after chemotherapy than that before chemotherapy(14.74%vs.61.05%,P<0.05).The efficacy of chemotherapy was negatively correlated with the positive expression of CTC after chemotherapy(P<0.001).COX regression analysis found that clinical stageⅢ,positive EGFR and CTC after chemotherapy were independent risk factors of progression of triple negatively breast cancer(P<0.05).PFS of patients at clinical stageⅠ,stageⅡ,and stageⅢdecreased in order(P<0.05).PFS of EGFR positive patients was shorter than that of EGFR negative patients(P<0.05).PFS of CTC positive patients after chemotherapy was shorter than that of CTC negative patients after chemotherapy(P<0.05).Conclusion The positive expression of EGFR before chemotherapy and the positive expression of CTC after chemotherapy are related to the poor survival prognosis of patients with triple negative breast cancer.The lower the positive detection rate of CTC after chemotherapy,the better the efficacy of chemotherapy.