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首页> 外文期刊>Modern Pathology >Genetic and clinical correlates of entosis in pancreatic ductal adenocarcinoma
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Genetic and clinical correlates of entosis in pancreatic ductal adenocarcinoma

机译：胰腺导管腺癌中卵泡遗传和临床关联

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Entosis is a type of regulated cell death that promotes cancer cell competition. Though several studies have revealed the molecular mechanisms that govern entosis, the clinical and genetic correlates of entosis in human tumors is less well understood. Here we reviewed entotic cell-in-cell (CIC) patterns in a large single institution sequencing cohort (MSK IMPACT clinical sequencing cohort) of more than 1600 human pancreatic ductal adenocarcinoma (PDAC) samples to identify the genetic and clinical correlates of this cellular feature. After case selection, 516 conventional PDACs and 21 ASCs entered this study and ~45,000 HPFs (median 80 HPFs per sample) were reviewed; 549 entotic-CICs were detected through our cohort. We observed that entotic-CIC occurred more frequently in liver metastasis compared with primary in PDAC. Moreover, poorly differentiated adenocarcinoma or adenosquamous carcinoma had more entotic-CIC than well or moderately differentiated adenocarcinoma. With respect to genetic features TP53 mutations, KRAS amplification, and MYC amplification were significantly associated with entosis in PDAC tissues. From a clinical standpoint entotic CICs were independently associated with a poor prognosis by multivariate Cox regression analysis when considering all cases or primary PDACs specifically. These results provide a contextual basis for understanding entosis in PDAC, a highly aggressive cancer for which molecular insights are needed to improve survival.
机译：entis是一种促进癌细胞竞争的受管制细胞死亡。虽然有几项研究揭示了治理卵体的分子机制，但人类肿瘤中卵泡的临床和遗传相关性较小地理解。在这里，我们在大于1600人胰腺导管腺癌（PDAC）样品的大单一机构测序队列（MSK冲击临床测序队列）中审查了偶然的细胞内（CIC）模式，以确定该细胞特征的遗传和临床关联。在案例选择后，516次常规PDAC和21个ASC进入本研究，综述了〜45,000个HPF（每个样本中位数80 HPF）;通过我们的队列检测到549个敌意。我们观察到与PDAC中的初级相比，肝脏转移中的敌人CIC更频繁地发生。此外，腺癌或腺细胞正癌癌的差异不良，比良好或中等分化的腺癌具有更大的突出菌性CIC。关于遗传特征TP53突变，KRA扩增和MyC扩增与PDAC组织中的卵巢显着相关。从临床的角度来看，在考虑所有病例或初级PDACs的情况下，多元COX回归分析的预后差异独立相关。这些结果为理解PDAC的卵泡提供了一种上下文基础，这是一种高度侵略性的癌症，用于改善存活的分子见解。

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