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目的三阴性乳腺癌(triple negative breast cancer,TNBC)具有侵袭性强、远处转移率高的病理特点。但TNBC亦具有明显的异质性,因此准确评估TNBC的预后,对指导临床个体化治疗具有重要的意义。本研究采用临床常用指标和分子标志物建立分子标记列线图模型,分析和探讨其预测TNBC预后的能力。方法选取2007-03-01-2012-01-31广东省妇幼保健院有完整随访的TNBC手术标本199例,应用免疫组织化学法(immunohistochemistry,IHC)检测癌组织中雄激素受体(androgen receptor,AR)、表皮生长因子受体(epiderrmal growth factor receptor,EGFR)、细胞角蛋白(cytokeratin 5/6,CK5/6)、p53、Ki-67的表达。采用SPSS 22.0统计软件包进行数据分析,建立分子标记列线图模型并分析其对TNBC预后的预测能力。结果Kaplan-Mier单因素生存分析显示,EGFR阴性表达者无病生存期(disease free survival,DFS)及总生存期(overall survival,OS)均优于阳性表达者,P值分别为0.007和0.006;AR阳性表达者DFS及OS均优于阴性表达者,P值分别为0.047和0.041;CK5/6阴性表达者DFS优于阳性表达者(P=0.045),但CK5/6阳性表达与阴性表达者OS差异无统计学意义,P=0.104;p53及Ki-67阳性表达与阴性表达者DFS差异无统计学意义,P值分别为0.075和0.059;3年OS差异亦无统计学意义,P值分别为0.058和0.307。Cox回归多因素分析显示,T分期、N分期、AR和EGFR均为TNBC的DFS和OS独立影响因素。以T分期、N分期、AR、EGFR建立列线图模型,列线图预测TNBC 3年DFS的C-index为0.702,95%CI=0.650~0.754;预测OS的C-index为0.698,95%CI=0.631~0.764。校准曲线显示,列线图预测与实际观察的3年DFS及OS均有较好的一致性。结论 AR或EGFR表达可作为TNBC生存预后判断的独立指标。基于“T分期、N分期、AR和EGFR”建立的列线图模型,有可能成为TNBC预后判断的重要预测模型。
Objective Triple negative breast cancer (TNBC) has the characteristics of strong invasion and high distant metastasis. However, TNBC also has obvious heterogeneity. Therefore, accurately assessing the prognosis of TNBC is of great significance in guiding clinical individualized treatment. In this study, we established a molecular marker nomogram model using the commonly used clinical indicators and molecular markers to analyze and explore its ability to predict the prognosis of TNBC. Methods A total of 199 TNBC cases with complete follow-up were selected from March 2007 to January 31,2012 in Guangdong MCH hospital. The expression of androgen receptor in cancer tissue was detected by immunohistochemistry (IHC) AR), epidermal growth factor receptor (EGFR), cytokeratin 5/6, CK5 / 6, p53 and Ki-67. SPSS 22.0 statistical package was used for data analysis, and molecular marker nomogram model was established and its predictive ability of TNBC prognosis was analyzed. Results Kaplan-Mier univariate survival analysis showed that the EGFR negative expression of the disease-free survival (DFS) and overall survival (OS) were better than the positive expression, P values were 0.007 and 0.006; The positive rates of DFS and OS in AR-positive patients were significantly higher than those in negative ones (P = 0.047 and 0.041, respectively). The positive rates of DFS in CK5 / 6 negative patients were significantly higher than those in negative ones OS was not significantly different (P = 0.104). There was no significant difference in the expression of p53 and Ki-67 between the positive and negative DFS (P = 0.075 and 0.059, respectively) 0.058 and 0.307. Cox regression multivariate analysis showed that T stage, N stage, AR and EGFR were independent factors of DFS and OS of TNBC. The C / index of TNBC 3-year DFS was 0.702, 95% CI = 0.650-0.754, and C-index of OS was 0.698, 95% CI = 0.631 ~ 0.764. The calibration curve shows that there is good agreement between the nomogram and the observed 3-year DFS and OS. Conclusion The expression of AR or EGFR can be used as an independent indicator of TNBC prognosis. The nomogram model based on “T staging, N staging, AR and EGFR ” may be an important predictor of TNBC prognosis.