乳腺癌MRI影像表现与生物因子、分子分型及病理组织分级相关性研究

发布时间：2018-03-19 19:00

  本文选题：乳腺癌　切入点：动态磁共振成像　出处：《广州医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：研究目的:探讨乳腺癌磁共振影像学特征与分子生物学指标、分子亚型及WHO组织学分级之间的相关性。材料与方法:本研究回顾性分析了从2015年3月至2017年2月在广州医科大学附属第二医院通过穿刺或手术病理证明为乳腺癌的患者总共90例。全部病人均为单侧乳腺发病,其中单发肿块者75例,多发肿块者15例,年龄区间为29~87岁,平均年龄为54岁。所有病人在术前未进行任何相关治疗且术前均成功行乳腺磁共振动态增强检查(DCE-MRI),术后病理切片以及免疫组化标记物检查。所有影像学相关参数,是由两位具有五年以上临床工作经验的放射科主治医师依据MRI乳腺影像报告和数据系统(BI-RADS)来进行判读,影像内容包括肿瘤的形态学特征:肿块的直径(2cm或≤2cm),肿块形状(类圆形,分叶状,不规则状),肿块边缘(光滑,毛刺,不光整),肿块的强化方式(均匀,混杂,环形)。血流动力学特征:时间信号曲线(time-signal intensity curve,TIC),即I型:呈缓慢持续上升;II型:早期上升迅速,而于中后期速度维持在平稳水平;III型:注入对比剂后病灶早期即可明显强化,而中后期病灶的信号强度呈逐步下降;肿瘤的信号增强率,达峰时间、流出率等指标。将病人术后的病理资料进行分析和记录,其中包括肿瘤淋巴结转移状况,WHO分级情况;通过免疫组化所获取的生物学因子表达情况和分子亚型分类,包括雌激素受体(ER),孕激素受体(PR),原癌基因人类表皮生长因子受体-2(C-erb B-2),抑癌基因P53,细胞增殖抗原标记物(Ki-67),TopoⅡα同工酶等。数据分析方面,应用SPSS 22.0软件,计量资料采取均数±标准差(x±s)表述,行非参数Spearman相关性检验和二分类Logistic回归分析,检验显著性以α=0.05为水准,以P0.05认为具有统计学差异。结果单发肿块75例(83%),多发肿块15(17%)例,形态学表现为类圆形33例(37%),分叶状29例(32%),不规则者28例(31%);肿瘤边缘光滑者占31例(34%),边缘不光整约20例(22%),边缘毛刺征者达39例(43%);肿瘤的强化方式,肿块呈明显均匀强化者48例(53%),混杂式强化者约29例(32%),环形强化者13例(14%)。时间-信号曲线类型:Ⅱ型47例(52.2%),Ⅲ型43例(47.8%)。最大强化率值为93.5%~494.53%,平均值为(271.92±62.30)%。病灶达峰时间值为58.21~414.89s,平均达峰时间值为(196.69±100.28)s,病理及免疫组化结果:其中80例乳腺浸润性导管癌(89.0%),1例乳腺粘液腺癌(1.1%),3例乳腺高级别导管内癌(3.3%),乳腺浸润性小叶癌者4例(4.4%),乳腺浸润性乳头状癌者2例(2.2%)。WHO组织分级:Ⅰ级2例(2.6%),Ⅱ级33例(42.9%),Ⅲ级42例(54.5%);淋巴结转移阳性者35例(48.9%),淋巴结转移阴性者55例(61.1%)。ER阳性表达58例(64.4%),ER阴性表达32例(35.6%);PR阳性表达45例(50%),PR阴性表达45例(50%);C-erb B-2阳性表达29例(48.3%),C-erb B-2阴性表达61例(51.7%);p53阳性表达22例(24.4%),p53阴性表达68例(75.6%);TopoⅡα阳性表达59例(65.5%),TopoⅡα阴性表达31例(34.5%);Ki-67阳性表达67(74.4%),Ki-67阴性表达23例(25.6%)。(1)乳腺肿瘤的大小:肿块的大小与ER的表达呈负相关(r=-0.264,p=0.012),与P53(r=0.22,p=0.03)及C-erb B-2(r=0.272,p=0.032)表达呈正相关。(2)肿瘤的形态:肿瘤的形态与ER(r=-0.273,p=0.009)及PR(r=-0.226,p=0.032)表达呈负相关,与C-erb B-2(r=0.220,p=0.037)表达呈正相关。(3)肿瘤的边缘:肿瘤的边缘与ER(r=0.320,p=0.002)及PR(r=0.209,p=0.048)表达呈正相关。(4)肿瘤的内部强化方式及强化曲线类型与各生物因子间无明显相关性。(5)淋巴结转移与p53(r=0.275,p=0.014)及Ki-67(r=0.237,p=0.026)表达呈正相关。(6)达峰时间与TopoⅡα(r=-0.240,p=0.04)及Ki-67表达(r=-0.296,p=0.01)呈负相关,而信号增强率及流出率与生物因子无统计学差异。(7)分子分型与肿瘤的大小显著正相关(r=0.239,p=0.041),即Her-2过表达型乳腺肿瘤的直径较其他类型大。(8)乳腺癌的WHO分级同肿块内部的强化方式呈显著负相关(r=-0.235,p=0.043),即肿块的组织学分级越高,肿瘤的强化方式越趋向于混杂式强化。(9)二分类Logistic回归分析显示HER-2阳性表达者肿块为较大直径的风险是HER-2表达阴性者的5.71倍,p53表达阳性者出现较大直径的风险是p53表达阴性者的5.403倍,TopoⅡα表达阳性者出现较大直径的风险是P53表达阴性者的3.565倍。结论:本研究认为乳腺癌MRI影像学表现与分子生物学指标、WHO分级及分子分型间存在一定的相关性,因此可进一步应用影像学检查方法来间接反映乳腺癌的生物学行为,为乳腺癌患者制定合理的个体化诊疗方案提供更多参考依据。
[Abstract]:Objective: To investigate the characteristics and molecular biology of breast cancer magnetic resonance imaging, correlation between the classification of molecular subtypes and WHO. Materials and methods: This was a retrospective study from March 2015 to February 2017 through the puncture or surgical pathology proved breast cancer patients with a total of 90 patients in the Second Affiliated Hospital of Guangzhou Medical University. All patients were unilateral breast disease, including 75 cases of single tumor, 15 cases of multiple masses, age range 29~87 years old, the average age was 54 years. All patients in the preoperative without any treatment and before surgery were successfully performed breast dynamic enhanced magnetic resonance examination (DCE-MRI), postoperative pathology biopsy and immunohistochemical marker examination. All the parameters of imaging, by two with more than five years working experience in clinical radiology physician on the basis of MRI breast imaging reporting and data system (BI-RADS ) for interpretation, image content including morphological characteristics of tumor mass diameter (2cm or 2cm), mass shape (round, lobulated, irregular), mass margins (smooth, burr, not finishing), enhancement mass (uniform, hybrid, ring). Hemodynamic characteristics: time signal curve (time-signal intensity curve, TIC), namely I type: a slow rising; type II: early rising rapidly, and in the middle and late rate remained at a steady level; type III: early lesions after injection of contrast agent can obviously strengthen, and the signal intensity in the late lesions showed a gradual decline in tumor signal; enhanced rate, peak time, flow rate and other indicators. The pathological data of patients were analyzed and recorded, including tumor lymph node metastasis, WHO classification; expression and molecular subtype classification by biological factor Immunohistochemistry was taken, including female 婵，

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