目的 探讨MRI联合临床病理特征在乳腺癌人表皮生长因子受体2(human epidermal growth factor receptor 2,HER-2)表达状态中的鉴别诊断价值,尤其是在HER-2低表达乳腺癌中的鉴别诊断价值.材料与方法 回顾性分析2018年1月至2019年12月在复旦大学附属肿瘤医院经病理证实为乳腺癌的患者治疗前乳腺MRI图像,205例患者均行双侧乳腺平扫及增强MRI检查.根据免疫组织化学和荧光原位杂交结果将HER-2状态分为HER-2阴性(包括零、低表达)和阳性(过表达).分析各组临床病理特征及MRI特征,临床病理特征包括年龄、月经状态、雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)、激素受体(hormone receptor,HR)、分子分型和Ki-67水平.MRI特征包括纤维腺体类型、背景实质强化、多灶或多中心、瘤内T2WI高信号、瘤周水肿、病灶类型、病灶大小、肿块形状、边缘、内部强化模式、非肿块强化分布及内部强化模式.单因素分析中,对于HER-2阴、阳性组间比较,年龄采用独立样本t检验,病灶大小采用Mann-Whitney U检验,其余临床病理特征及MRI特征采用χ2检验;对于HER-2零、低和过表达组的比较,年龄采用单因素方差分析,病灶大小采用Kruskal-Wallis H检验;其余临床病理特征及MRI特征采用χ2检验.多因素分析采用二元logistic回归分析,用受试者工作特征曲线下面积(area under the curve,AUC)、敏感度和特异度评价模型的诊断效能.结果 HER-2阴性中零表达59例、低表达79例,HER-2阳性(过表达)67例.HER-2阴性与阳性组临床病理特征中,ER、PR、HR和分子分型差异有统计学意义(P均＜0.001),MRI特征中肿块边缘差异有统计学意义(P=0.020).进一步比较HER-2低表达组与零表达组、HER-2低表达组与过表达组,临床病理特征中,ER、PR、HR、分子分型和Ki-67水平(以中位数40％为截断值)组间差异具有统计学意义(ER、PR、HR、分子分型:P均＜0.001;Ki-67:P＜0.001,P=0.037);MRI特征中,瘤内T2WI高信号与肿块形状组间差异具有统计学意义(瘤内T2WI高信号:P=0.031,P=0.011;肿块形状:P=0.012,P=0.025),且肿块边缘在HER-2低表达与零表达组间差异有统计学意义(P=0.036).联合临床病理和MRI特征的多因素分析提示,PR状态、Ki-67水平及肿块形状是鉴别乳腺癌HER-2低表达与零表达的独立预测因素,AUC、敏感度和特异度分别为0.772、79.7％和70.9％;PR状态及瘤内T2高信号是鉴别HER-2低表达与过表达的独立预测因素,AUC、敏感度、特异度分别为0.793、69.8％和76.1％.结论 MRI影像特征对乳腺癌HER-2表达状态具有鉴别诊断价值,尤其在HER-2低表达与零表达或过表达乳腺癌鉴别诊断中.联合临床病理特征,PR阳性、Ki-67低于40％、肿块形状不规则和瘤内T2WI高信号可提示HER-2低表达乳腺癌.
Diagnostic value of MRI features combined with clinicopathologic features in predicting the expression of human epidermal growth factor receptor 2 in breast cancer
Objective:To explore the value of magnetic resonance imaging(MRI)features combined with clinicopathologic features in distinguishing human epidermal growth factor receptor 2(HER-2)expression status,especially in HER-2-low breast cancer.Materials and Methods:The pre-treatment breast MRI images of 205 patients with pathologically confirmed breast cancer from January 2018 to December 2019 at Fudan University Shanghai Cancer Center were retrospectively analyzed.All patients underwent a bilateral breast scan and a dynamic contrast enhancement MRI.HER-2 status was categorized into HER-2 negative(including HER-2-zero and HER-2-low)and HER-2 positive based on immunohistochemistry and fluorescence in situ hybridization results.Clinicopathologic features and MRI features were analyzed in each group.Clinicopathologic features included age,menstrual status,estrogen receptor(ER),progesterone receptor(PR),hormone receptor(HR),molecular subtypes and Ki-67 level.MRI features included fibroglandular tissue,background parenchymal enhancement,multifocal or multicentric,intratumoral T2WI high signal,peritumoral edema,lesion type,lesion size,shape,margin and internal enhancement pattern of the mass,and distribution and internal enhancement pattern of non-mass enhancement.In the univariate analysis,for the comparison between HER-2 negative and positive groups,an independent sample t-test was used for age,a Mann-Whitney U test was used for lesion size,and a χ2 test was used for the remaining clinicopathologic and MRI features.For the comparison of HER-2 zero,low,and overexpression groups,a one-way analysis of variance was used for age,a Kruskal-Wallis H test was used for lesion size,and a χ2 test was used for the remaining clinicopathologic and MRI features.Multifactorial analysis was performed by binary logistic regression analysis,and the diagnostic efficacy of the model was evaluated by area under the curve(AUC),sensitivity and specificity of the receiver operating characteristic.Results:There were 67 HER-2-positive(HER-2-overexpression),59 HER-2-zero and 79 HER-2-low cases.Between the HER-2-negative and positive group,the difference in clinicopathologic features of ER,PR,HR,and molecular typing were statistically significant(all P＜0.001),and the differences in the margin of the mass in MRI features were statistically significant(P=0.020).Further comparing the HER-2 low with HER-2-zero group or HER-2-overexpression group,the differences in clinicopathologic features were statistically significant in ER,PR,HR,molecular subtypes,and Ki-67 levels(with a cutoff value of 40％of the median)between HER-2-low and HER-2-zero or HER-2-overexpression group(ER,PR,HR,and molecular subtypes:all P＜0.001;Ki-67:P＜0.001,P=0.037);among the MRI features,the differences in the intratumoral T2WI hyperintensity and mass shape were statistically significant between HER-2-low and HER-2-zero or HER-2-overexpression group(intratumoral T2WI hyperintensity:P=0.031,P=0.011;mass shape:P=0.012,P=0.025),and the difference in the mass margin was statistically significant between HER-2-zero and HER-2-low group(P=0.036).In the multifactorial analysis combining clinicopathologic and MRI features,PR status,Ki-67 and mass shape were independent predictors to distinguish HER-2-low and-zero expression,with an AUC,sensitivity,and specificity of 0.772,79.7％,and 70.9％,respectively;and PR status and intratumoral T2WI hyperintensity were independent predictors to distinguish HER-2-low versus-overexpression,with an AUC,sensitivity,and specificity of 0.793,69.8％and 76.1％,respectively.Conclusions:MRI features have a differential diagnostic value for HER-2 expression status in breast cancer,especially in distinguishing HER-2 low-expression and HER-2-zero or-overexpression status.Combining clinicopathologic features and MRI features,PR positivity,Ki-67 lower than 40％,irregular mass shape,and intratumoral T2WI hyperintensity can indicate HER-2 low-expression breast cancer.
万方数据
维普
