Genetic and clinical correlates of entosis in pancreatic ductal adenocarcinoma

被引：47

作者：

Hayashi, Akimasa ^{[1
,2
]}

Yavas, Aslihan ^{[1
,3
]}

McIntyre, Caitlin A. ^{[1
,2
]}

Ho, Yu-jui ^{[4
]}

Erakky, Amanda ^{[1
]}

Wong, Winston ^{[5
]}

Varghese, Anna M. ^{[5
]}

Melchor, Jerry P. ^{[1
,2
]}

Overholtzer, Michael ^{[6
]}

O'Reilly, Eileen M. ^{[1
,5
]}

Klimstra, David S. ^{[1
,3
]}

Basturk, Olca ^{[3
]}

Iacobuzio-Donahue, Christine A. ^{[1
,2
,3
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, David M Rubenstein Ctr Pancreat Canc Res, Sloan Kettering Inst, 1275 York Ave, New York, NY 10021 USA

[2] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Human Oncol & Pathogenesis Program, 1275 York Ave, New York, NY 10021 USA

[3] Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA

[4] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Canc Biol & Genet Program, 1275 York Ave, New York, NY 10021 USA

[5] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA

[6] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Cell Biol Program, 1275 York Ave, New York, NY 10021 USA

来源：

MODERN PATHOLOGY | 2020年 / 33卷 / 09期

关键词：

D O I：

10.1038/s41379-020-0549-5

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

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 similar to 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.

引用

页码：1822 / 1831

页数：10

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