Genetic and clinical correlates of entosis in pancreatic ductal adenocarcinoma Journal Article
| Authors: | Hayashi, A.; Yavas, A.; McIntyre, C. A.; Ho, Y. J.; Erakky, A.; Wong, W.; Varghese, A. M.; Melchor, J. P.; Overholtzer, M.; O’Reilly, E. M.; Klimstra, D. S.; Basturk, O.; Iacobuzio-Donahue, C. A. |
| Article Title: | Genetic and clinical correlates of entosis in pancreatic ductal adenocarcinoma |
| Abstract: | 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. © 2020, The Author(s). |
| Keywords: | controlled study; human tissue; aged; cancer surgery; genetic trait; human cell; major clinical study; sequence analysis; clinical feature; histopathology; patient selection; cancer patient; antineoplastic agent; genetic analysis; gene amplification; tumor differentiation; cohort analysis; protein p53; pancreas carcinoma; tissue section; liver metastasis; lung metastasis; proportional hazards model; myc protein; cancer cell; cell migration; pancreas adenocarcinoma; pancreatectomy; adenosquamous carcinoma; cancer tissue; neoadjuvant chemotherapy; k ras protein; peritoneum metastasis; predictive value; correlational study; diagnostic test accuracy study; entosis; cancer prognosis; adjuvant chemoradiotherapy; human; male; female; priority journal; article; regulated cell death |
| Journal Title: | Modern Pathology |
| Volume: | 33 |
| Issue: | 9 |
| ISSN: | 0893-3952 |
| Publisher: | Nature Research |
| Date Published: | 2020-09-01 |
| Start Page: | 1822 |
| End Page: | 1831 |
| Language: | English |
| DOI: | 10.1038/s41379-020-0549-5 |
| PUBMED: | 32350415 |
| PROVIDER: | scopus |
| PMCID: | PMC7452867 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 October 2020 -- Source: Scopus |
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