乳腺浸润性小叶癌组织Ki-67表达与临床病理特征相关性分析

Analysis between prognosis and expression of Ki-67 with different clinicopathologic features of breast invasive lobular carcinoma

目的浸润性小叶癌(invasive lobular carcinoma,ILC)组织中Ki-67表达的研究较少,对其预后预测价值尚需进一步文献支持。本研究探讨ILC组织不同临床病理特征下Ki-67表达差异及其与预后的关系。方法收集天津医科大学肿瘤医院2003-01-10-2012-12-15收治的381例乳腺ILC患者的临床病理资料,分析Ki-67与其临床病理特征的相关性。分析不同年龄、月经状态、体质量指数、家族史、肿瘤大小、淋巴结状态、病理学分期、组织学分型、ER状态、PR状态、HER-2状态和p53状态下,Ki-67表达与预后的关系。结果 381例ILC组织中Ki-67低表达76例(19.9%),中表达91例(23.9%),高表达214例(56.2%)。在不同肿物大小(χ~2=12.524,P=0.014)、腋窝淋巴结情况(χ~2=6.114,P=0.047)、临床分期(χ~2=10.434,P=0.034)、ER表达(χ~2=6.339,P=0.041)和组织学类型(χ~2=78.288,P<0.001)情况下,Ki-67表达差异有统计学意义。Ki-67表达与肿物大小(r=0.168,P=0.001)、腋窝淋巴结情况(r=0.108,P=0.036)、临床分期(r=0.149,P=0.004)和组织学类型(r=0.532,P<0.001)呈正相关。Ki-67表达与ER表达呈负相关,r=-0.112,P=0.029。在肿瘤大小2~5cm、有腋窝淋巴结转移及临床Ⅱ期ILC组织中,Ki-67表达对患者总生存(overall survival,OS)差异有统计学意义,P<0.05;而对无病生存(disease-free survival,DFS)差异无统计学意义,P>0.05。Cox多因素分析显示,有无淋巴结转移(P=0.000)是ILC总生存的独立预后因素,而肿瘤大小、临床分期和Ki-67表达水平不是影响ILC总生存的独立预后因素,P>0.05。结论乳腺ILC组织中Ki-67高表达。就诊时肿物越大、有腋窝淋巴结转移和临床分期越高,Ki-67表达水平越高,而ER表达水平越高,Ki-67表达水平越低,肿物大小2~5cm、有腋窝淋巴结转移及临床Ⅱ期,即中低度恶性ILC组织中Ki-67表达对患者预后有一定的预测价值,但不是独立预后因素,Ki-67对ILC预后预测作用尚需进一步研究。

OBJECTIVE There is few research about Ki-67 expression in invasive lobular carcinoma,and its prog- nostic value still needs further literature support. The aim of the study was to analyze the relationship between prognosis and expression of Ki-67 with different clinicopathologic features of ILC. METHODS Clinical data of 381 patients with resectable breast ILC in Tianjin Medical University Cancer Institute and Hospital were collected from January 10,2003 to December 15,2012. RESULTS There was 76 cases （19.9%） with Ki-67 low expression,while Ki-67 moderate expression was in 91 cases （23.9%） and Ki-67 high expression was in 214 cases （56.2%） in the whole group of 381 ILC cases. The result showed statistical differences among different Ki-67 expression level regarding tumor size,lymph node metastasis,clinical stage,ER expression and histological classification （P〈0.05）. There was positive correlation between Ki-67 expression and tumor size（r=0. 168,P= 0. 001）,lymph node metastasis（r=0. 108,P= 0. 036）,clinical stage（r= 0. 149, P=0. 004）and histological classification（r=0. 532, P〈0. 001）. The correlation between Ki-67 expression and ER expression （r=-0. 112,P=0. 029） was opposite. The expression of Ki-67 in T2 stage ILC,lymph node positive or stage Ⅱ had significant influence on the OS（P〈0.05）. Multi-factor analysis showed that Ki-67 was not independent pronostic for the overall of patients. CONCLUSIONS Ki-67 is highly expressed in ILC. The large the tumor size,with axillary lymph node invasion and the higher clinical stage, the higher the Ki-67 expression level is. The non-classical ILC has higher Ki-67 expression. The higher the ER expressed, the lower the Ki-67 expression was. Ki-67 expression of ILC with tumor more than 2 cm and less than 5 cm,clinical stage Ⅱ and positive lymph node has a significant impact on the survival of patients. Ki-67 has more predictive value for patients with moderate and low-grade malignant ILC. The higher Ki-67 expressed, the worse the prognosis of patients is.