HER2双重不确定性乳腺癌的困境基因组谱分析及其治疗意义

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  摘要:按照2013版美国临床肿瘤学会/美国病理学家协会(American Society of Clinical Oncology/College of American Pathologists,ASCO/CAP)HER2评估指南,原位杂交检测后HER2不确定性乳腺癌的数量较以往增加,也就是说,HER2“双重不确定性”(不确定性的蛋白表达和不确定性的基因拷贝数)。本文对45例双重不确定性的癌进行Prosigna分析。27例病例进行了雌激素受体(estrogen receptor,ER)阳性/HER2阳性(N=22)和ER阳性/HER2阴性(N =22)对照组间差异基因的表达检测。45例病例中的29例进行了14个基因panel的靶向测序分析。随后在一个给予含曲妥珠单抗化疗处理的HER2双重不确定性乳腺癌独立样本系列中评估了病理完全缓解率。所有患者均为ER阳性,Ki67平均指数为书28%。双重不确定性癌主要是管腔B型(76%); 9例(20%) 为管腔A型,2例为HER2(4%)增强型。Prosigna分析结果显示,即使肿瘤很小(<2cm)、淋巴结阴性/微转移和/或2级,多数(73%)乳腺癌患者仍显示高复发风险。HER2双重不确定性乳腺癌存在TP53(6/29,20%)、PIK3CA(3/29,10%)、HER2(1/29, 3%)和 MAP2K4 (1/29,3%)基因的突变。与来自METABRIC的ER阳性/HER2阴性乳腺癌相必,HER2双重不确定性乳腺癌发生TP53突变频率更高,PIK3CA突变频率更低(P<0.05)。未观察到与ER阳性/HER2阳性乳腺癌之间的显著差异。HER2不确定患者的病理完全缓解率较HER2阳性组更低(10%vs. 60%, P = 0.009)。HER2双重不确定性乳腺癌主要为管腔B型,复发风险高。转录组学分析将其中一个亚类定为HER2增强型。HER2双重不确定性病例中可出现HER2突变。
  关键词:乳腺癌,HER2,不确定的结果,分子亚型,复发风险,突变
(Am J Surg Pathol 2018;42:1190-1200)
美国外科病理学杂志中文版2019年第2期全文No.5
(周 雪/王 蔚  翻译  梁 莉  审校)










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