表达HepPar1的肺固体和颗粒性腺癌:高度侵略性的瘤,表现出线粒体适应STK11突变而不是肝细胞分化
Christopher A Febres-Aldana1, Chad M Vanderbilt2, Rania Aly2
1Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
概括
肺腺癌中孤立的HepPar1表达 (LUAD) 表示线粒体适应STK11突变,而不是肝细胞分化. 这些称为SAGA的瘤具有侵略性,并带来了诊断挑战.
科学领域:
- 在瘤学瘤学.
- 病理学 病理学 病理学
- 基因组学就是基因组学.
背景情况:
- 肝炎性肺癌是由不同的肝细胞分化定义的,通常只表达HepPar1 (肝细胞标记物).
- 在STK11突变的肺腺癌 (LUAD) 中HepPar1/CPS1的积累表明基因型相关的代谢适应.
- 对肝癌肺癌分类的影响仍然未被探索.
研究的目的:
- 执行与孤立的HepPar1表达的瘤的临床病理学和基因组分析.
- 调查HepPar1表达,STK11突变和LUAD中的瘤行为之间的关系.
- 澄清LUAD中HepPar1表达的诊断和预后意义.
主要方法:
- 临床病理学和基因组分析17个瘤与孤立的HepPar1表达.
- 对肝细胞和肺细胞标记物的评估 (AFP,阿尔金纳1,Glypican3,白蛋白-ISH,TTF1,纳普辛A).
- 为STK11突变/损失进行下一代测序,并与超过2.5K个未经选择的LUAD病例进行比较.
主要成果:
- 瘤是HepPar1阳性的,但对其他肝细胞标记物是负的,具有焦点粘素和可变的肝细胞形态.
- 观察到不变的STK11突变/损失 (P<0.00001),以及令人丧的患者存活率 (中位数5.8个月).
- 具有HepPar1表达的常规LUAD也显示STK11突变/损失和不良预后.
结论:
- 在LUAD中孤立的HepPar1表达表明线粒体适应STK11突变,而不是真正的肝细胞分化.
- 表达HepPar1的固体和颗粒性腺癌 (SAGA) 是一个不分化的LUAD变体.
- 由于攻击性行为,独特的病原组学和诊断挑战,识别SAGA至关重要.
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