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HER2扩增亚型的肝内胆固醇癌表现出高突变负担和T细胞耗尽的微环境

Xiaohong Pu¹, Lin Li¹, Feng Xu²

¹Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Drum Tower Hospital of Medical School, Nanjing University, Nanjing, 210008, Jiangsu Province, China.

Journal of cancer research and clinical oncology

|August 28, 2024

概括

光在位杂交 (FISH) 是HER2在肝脏内胆管癌 (ICC) 的评估的黄金标准. 增强HER2的ICC显示出更糟糕的预后,更高的瘤突变负担和免疫抑制的微环境.

科学领域:

在瘤学瘤学.
分子诊断学分子诊断
癌症基因组学癌症基因组学

背景情况:

肝脏内胆管癌 (ICC) 是一种罕见且具有攻击性的胆道癌.
准确的HER2 (人类表皮生长因子受体2) 状态的确定对于在各种癌症中选择向治疗至关重要.
在ICC中缺乏对HER2的标准化解释,这阻碍了临床应用.

研究的目的:

在ICC中建立HER2基因和蛋白质状态解释的统一标准.
研究HER2阳性ICC的临床病理学,分子和免疫微环境特征.

主要方法:

使用免疫组织化学 (IHC) 和光在位杂交 (FISH) 对HER2状态的304个ICC样本的分析.
下一代测序用于全面的临床病理学,分子遗传学和RNA表达概况.
IHC和多重免疫光染色以评估瘤微环境.

主要成果:

根据FISH标准 (HER2/CEP17比率≥2.0或HER2拷贝数≥4.0;或HER2拷贝数≥6.0) 在4.27%的ICC病例中发现了HER2放大.
在ICC中观察到FISH和IHC之间对HER2评估的协议较差.
在HER2增强的ICC中,瘤突变负担较高,CD8+CTLA4+和CD8+FOXP3+细胞密度增加,表明T细胞耗尽.

结论:

在ICC中,FISH是HER2评估的首选黄金标准.
HER2基因增强的ICC与更差的预后,增加的突变负担和免疫抑制的瘤微环境有关,这表明潜在的治疗点.

关键词:

在HER2状态下.免疫组织化学免疫组织化学在光中,在现场混合化.在肝脏内发生的胆管癌,胆管癌.透T细胞的透情况

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