Undifferentiated Carcinoma with Osteoclast-like Giant Cells of the Pancreas: Molecular Genetic Analysis of 13 Cases

被引:4
作者
Hrudka, Jan [1 ]
Kalinova, Marketa [1 ,2 ]
Ciprova, Vanda [3 ]
Moravcova, Jana [1 ,4 ]
Dvorak, Radim [5 ]
Matej, Radoslav [1 ,3 ,6 ]
机构
[1] Charles Univ Prague, Univ Hosp Kralovske Vinohrady, Fac Med 3, Dept Pathol, Prague 10034, Czech Republic
[2] Univ Hosp Kralovske Vinohrady, Cent Labs, Prague 10034, Czech Republic
[3] Charles Univ Prague, Gen Univ Hosp, Fac Med 1, Dept Pathol, Prague 12800, Czech Republic
[4] Inst Clin & Expt Med, Clin & Transplant Pathol Ctr, Prague 14021, Czech Republic
[5] Charles Univ Prague, Univ Hosp Kralovske Vinohrady, Fac Med 3, Dept Gen Surg, Prague 10034, Czech Republic
[6] Charles Univ Prague, Thomayer Univ Hosp, Fac Med 3, Dept Pathol & Mol Med, Prague 14059, Czech Republic
关键词
pancreas; undifferentiated carcinoma with osteoclast-like giant cells; next-generation sequencing; DNA; PD-L1; EXPRESSION; REGULATES PD-L1; TUMOR; MUTATIONS; LANDSCAPE; CANCER; ORIGIN;
D O I
10.3390/ijms25063285
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) of the pancreas is a rare malignancy regarded as a subvariant of pancreatic ductal carcinoma (PDAC) characterized by variable prognosis. UCOGC shows a strikingly similar spectrum of oncogenic DNA mutations to PDAC. In the current work, we analyzed the landscape of somatic mutations in a set of 13 UCOGC cases via next-generation sequencing (NGS). We detected a spectrum of pathogenic or likely pathogenic mutations similar to those observed in PDAC following previously published results (10 KRAS, 9 TP53, 4 CDKN2A, and 1 SMAD4, CIC, GNAS, APC, ATM, NF1, FBXW7, ATR, and FGFR3). Our results support the theory that UCOGC is a variant of PDAC, despite its unique morphology; however, a UCOGC-specific genomic signature as well as predictive markers remain mainly unknown. Programmed death ligand 1 (PD-L1) status remains an important predictive marker based on previous studies.
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页数:11
相关论文
共 47 条
[1]   Validation of PD-L1 clone 22C3 immunohistochemical stain on two Ventana DISCOVERY autostainer models: detailed protocols, test performance characteristics, and interobserver reliability analyses [J].
Basu, Atreyee ;
Chiriboga, Luis ;
Narula, Navneet ;
Zhou, Fang ;
Moreira, Andre L. .
JOURNAL OF HISTOTECHNOLOGY, 2020, 43 (04) :174-181
[2]   Morphologic and Molecular Landscape of Pancreatic Cancer Variants as the Basis of New Therapeutic Strategies for Precision Oncology [J].
Bazzichetto, Chiara ;
Luchini, Claudio ;
Conciatori, Fabiana ;
Vaccaro, Vanja ;
Di Cello, Ilaria ;
Mattiolo, Paola ;
Falcone, Italia ;
Ferretti, Gianluigi ;
Scarpa, Aldo ;
Cognetti, Francesco ;
Milella, Michele .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2020, 21 (22) :1-25
[3]   Durable Response to PD-1 Blockade in a Patient With Metastatic Pancreatic Undi ff erentiated Carcinoma With Osteoclast-Like Giant Cells [J].
Besaw, Robert J. ;
Terra, Adrienne R. ;
Malvar, Grace L. ;
Chapman, Tobias R. ;
Hertan, Lauren M. ;
Schlechter, Benjamin L. .
JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK, 2021, 19 (03) :247-252
[4]  
Deckard-Janatpour K, 1998, ARCH PATHOL LAB MED, V122, P266
[5]   Undifferentiated Pancreatic Carcinoma With Osteoclast-Like Giant Cells: What Do We Know So Far? [J].
Demetter, Pieter ;
Marechal, Raphael ;
Puleo, Francesco ;
Delhaye, Myriam ;
Debroux, Sebastien ;
Charara, Fadi ;
Gomez Galdon, Maria ;
Van Laethem, Jean-Luc ;
Verset, Laurine .
FRONTIERS IN ONCOLOGY, 2021, 11
[6]   Targeting p53 for the treatment of cancer [J].
Duffy, Michael J. ;
Synnott, Naoise C. ;
O'Grady, Shane ;
Crown, John .
SEMINARS IN CANCER BIOLOGY, 2022, 79 :58-67
[7]   OSTEOCLASTIC GIANT-CELL TUMOR OF THE PANCREAS - AN IMMUNOHISTOLOGICAL STUDY AND REVIEW OF THE LITERATURE [J].
DWORAK, O ;
WITTEKIND, C ;
KOERFGEN, HP ;
GALL, FP .
PATHOLOGY RESEARCH AND PRACTICE, 1993, 189 (02) :228-231
[8]   Pharmacological rescue of mutant p53 conformation and function [J].
Foster, BA ;
Coffey, HA ;
Morin, MJ ;
Rastinejad, F .
SCIENCE, 1999, 286 (5449) :2507-2510
[9]   Cell cycle checkpoints and beyond: Exploiting the ATR/CHK1/WEE1 pathway for the treatment of PARP inhibitor-resistant cancer [J].
Gupta, Nitasha ;
Huang, Tzu-Ting ;
Horibata, Sachi ;
Lee, Jung-Min .
PHARMACOLOGICAL RESEARCH, 2022, 178
[10]   Maintenance therapies in metastatic pancreatic cancer: present and future with a focus on PARP inhibitors [J].
Hammel, Pascal ;
Vitellius, Carole ;
Boisteau, Emeric ;
Wisniewski, Mathilde ;
Colle, Elise ;
Hilmi, Marc ;
Dengremont, Christelle ;
Granier, Sandra ;
Turpin, Anthony ;
de Mestier, Louis ;
Neuzillet, Cindy .
THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY, 2020, 12