Lian J, Li R Q, Yan L, Bu P, Wang H W, Xi Y F
Department of Pathology, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan 030013, China.
Zhonghua Bing Li Xue Za Zhi. 2024 Sep 8;53(9):898-904. doi: 10.3760/cma.j.cn112151-20240531-00361.
To investigate the biological characteristics of triple negative breast cancer (TNBC) with low expression of HER2 (HER2-low). A total of 93 TNBC cases in Shanxi Cancer Hospital from 2017 to 2019 were collected and divided into HER2-negative and HER2-low groups according to HER2 expression status. The clinicopathological features and prognostic differences between the two groups were retrospectively analyzed and compared, and genetic detection of tumor tissues was performed to clarify somatic mutation status and differences between the two groups. Ninety-three patients aged 26 to 86 years were enrolled, including 60 patients in the HER2-negative group and 33 patients in the HER2-low group. The distribution of HER2-low in luminal androgen receptor (LAR) subtype (14/23, 60.87%) and non-LAR subtype (19/70, 27.14%) was significantly different (0.005). There were no significant differences in age, pT stage, histological grade, infiltration mode, lymph node metastasis and survival analysis. The expression of HER2-low in the tumor was heterogeneous, including different proportions of weak, weak to moderate intensity, and incomplete to intact membrane staining. With the change of the proportion of HER2-positive cells, the different distribution of those cells in the total tumor cells was noted, including cluster, mosaic and scattered patterns. The concentration and quality of DNA extracted from 71 of the 93 samples met the requirements for making libraries, including 43 in the HER2-negative group and 28 in the HER2-low group. Genetic mutations were mainly missense mutations, single nucleotide mutations, and point mutations in which base C was replaced by base T. There was no significant difference in genes with mutation frequency>3 times between the two groups. CTNNB1 and FGFR3 genes were only mutated in HER2-low group; while ALK, CYP2D6 and FAT1 genes were only mutated in HER2-negative group. HER2-low group included 18 HER2 1+ cases and 10 HER2 2+ cases. Genes with mutation frequency>3 times between the two groups included PIK3CA, TP53, SLX4, ATM and BRCA1. The mutation frequency of PIK3CA in HER2 2+ was significantly higher than that in HER2 1+ group (<0.05), and SLX4 gene was only mutated in HER2 1+ group. There are some differences of histological morphology and genetic variation between HER2-negative group and HER2-low group, and also differences in genetic variation between HER2 1+ and HER2 2+ in HER2-low group, which are helpful for more accurate stratification of TNBC and useful for finding the therapeutic target and precise treatment of HER2-low TNBC.
探讨人表皮生长因子受体2（HER2）低表达的三阴性乳腺癌（TNBC）的生物学特性。收集2017年至2019年山西省肿瘤医院的93例TNBC病例，根据HER2表达状态分为HER2阴性组和HER2低表达组。回顾性分析比较两组的临床病理特征及预后差异，并对肿瘤组织进行基因检测，明确两组的体细胞突变状态及差异。纳入93例年龄26至86岁的患者，其中HER2阴性组60例，HER2低表达组33例。HER2低表达在腔面雄激素受体（LAR）亚型（14/23，60.87%）和非LAR亚型（19/70，27.14%）中的分布差异有统计学意义（P=0.005）。两组在年龄、pT分期、组织学分级、浸润方式、淋巴结转移及生存分析方面差异无统计学意义。肿瘤中HER2低表达呈异质性，包括不同比例的弱阳性、弱至中度阳性以及不完整至完整的膜染色。随着HER2阳性细胞比例的变化，观察到这些细胞在肿瘤细胞总数中的不同分布，包括簇状、镶嵌状和散在状。93例样本中有71例提取的DNA浓度和质量符合建库要求，其中HER2阴性组43例，HER2低表达组28例。基因突变主要为错义突变、单核苷酸突变以及碱基C被碱基T取代的点突变。两组中突变频率>3次的基因差异无统计学意义。CTNNB1和FGFR3基因仅在HER2低表达组中发生突变；而ALK、CYP2D6和FAT1基因仅在HER2阴性组中发生突变。HER2低表达组包括18例HER2 1+病例和10例HER2 2+病例。两组中突变频率>3次的基因包括PIK3CA、TP53、SLX4、ATM和BRCA1。PIK3CA在HER2 2+中的突变频率显著高于HER2 1+组（P<0.05），SLX4基因仅在HER2 1+组中发生突变。HER2阴性组和HER2低表达组在组织形态学和基因变异方面存在一些差异，HER2低表达组中HER2 1+和HER2 2+在基因变异方面也存在差异，这有助于对TNBC进行更准确的分层，有助于寻找HER2低表达TNBC的治疗靶点并实现精准治疗。
