Pancreatic undifferentiated carcinoma with osteoclast-like giant cells is genetically similar to, but clinically distinct from, conventional ductal adenocarcinoma

Claudio Luchini; Antonio Pea; Gemma Lionheart; Andrea Mafficini; Alessia Nottegar; Nicola Veronese; Peter Chianchiano; Lodewijk A.A. Brosens; Michaël Noë; G. Johan A. Offerhaus; Raluca Yonescu; Yi Ning; Giuseppe Malleo; Giulio Riva; Paola Piccoli; Ivana Cataldo; Paola Capelli; Giuseppe Zamboni; Aldo Scarpa; Laura D. Wood

doi:10.1002/path.4941

Pancreatic undifferentiated carcinoma with osteoclast-like giant cells is genetically similar to, but clinically distinct from, conventional ductal adenocarcinoma

Claudio Luchini, Antonio Pea, Gemma Lionheart, Andrea Mafficini, Alessia Nottegar, Nicola Veronese, Peter Chianchiano, Lodewijk A.A. Brosens, Michaël Noë, G. Johan A. Offerhaus, Raluca Yonescu, Yi Ning, Giuseppe Malleo, Giulio Riva, Paola Piccoli, Ivana Cataldo, Paola Capelli, Giuseppe Zamboni, Aldo Scarpa, Laura D. Wood

School of Medicine

Research output: Contribution to journal › Article › peer-review

40 Scopus citations

Abstract

Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UCOGC) is currently considered a morphologically and clinically distinct variant of pancreatic ductal adenocarcinoma (PDAC). In this study, we report clinical and pathological features of a series of 22 UCOGCs, including the whole exome sequencing of eight UCOGCs. We observed that 60% of the UCOGCs contained a well-defined epithelial component and that patients with pure UCOGC had a significantly better prognosis than did those with an UCOGC with an associated epithelial neoplasm. The genetic alterations in UCOGC are strikingly similar to those known to drive conventional PDAC, including activating mutations in the oncogene KRAS and inactivating mutations in the tumor suppressor genes CDKN2A, TP53, and SMAD4. These results further support the classification of UCOGC as a PDAC variant and suggest that somatic mutations are not the determinants of the unique phenotype of UCOGC.

Original language	English (US)
Pages (from-to)	148-154
Number of pages	7
Journal	Journal of Pathology
Volume	243
Issue number	2
DOIs	https://doi.org/10.1002/path.4941
State	Published - Oct 2017

Keywords

PDAC variants
undifferentiated carcinoma with osteoclast-like giant cells
whole exome sequencing

ASJC Scopus subject areas

Pathology and Forensic Medicine

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10.1002/path.4941

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Luchini, C., Pea, A., Lionheart, G., Mafficini, A., Nottegar, A., Veronese, N., Chianchiano, P., Brosens, L. A. A., Noë, M., Offerhaus, G. J. A., Yonescu, R., Ning, Y., Malleo, G., Riva, G., Piccoli, P., Cataldo, I., Capelli, P., Zamboni, G., Scarpa, A., & Wood, L. D. (2017). Pancreatic undifferentiated carcinoma with osteoclast-like giant cells is genetically similar to, but clinically distinct from, conventional ductal adenocarcinoma. Journal of Pathology, 243(2), 148-154. https://doi.org/10.1002/path.4941

Luchini, C, Pea, A, Lionheart, G, Mafficini, A, Nottegar, A, Veronese, N, Chianchiano, P, Brosens, LAA, Noë, M, Offerhaus, GJA, Yonescu, R, Ning, Y, Malleo, G, Riva, G, Piccoli, P, Cataldo, I, Capelli, P, Zamboni, G, Scarpa, A & Wood, LD 2017, 'Pancreatic undifferentiated carcinoma with osteoclast-like giant cells is genetically similar to, but clinically distinct from, conventional ductal adenocarcinoma', Journal of Pathology, vol. 243, no. 2, pp. 148-154. https://doi.org/10.1002/path.4941

@article{281d658559714a718887da4d2acdcf33,

title = "Pancreatic undifferentiated carcinoma with osteoclast-like giant cells is genetically similar to, but clinically distinct from, conventional ductal adenocarcinoma",

abstract = "Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UCOGC) is currently considered a morphologically and clinically distinct variant of pancreatic ductal adenocarcinoma (PDAC). In this study, we report clinical and pathological features of a series of 22 UCOGCs, including the whole exome sequencing of eight UCOGCs. We observed that 60% of the UCOGCs contained a well-defined epithelial component and that patients with pure UCOGC had a significantly better prognosis than did those with an UCOGC with an associated epithelial neoplasm. The genetic alterations in UCOGC are strikingly similar to those known to drive conventional PDAC, including activating mutations in the oncogene KRAS and inactivating mutations in the tumor suppressor genes CDKN2A, TP53, and SMAD4. These results further support the classification of UCOGC as a PDAC variant and suggest that somatic mutations are not the determinants of the unique phenotype of UCOGC.",

keywords = "PDAC variants, undifferentiated carcinoma with osteoclast-like giant cells, whole exome sequencing",

author = "Claudio Luchini and Antonio Pea and Gemma Lionheart and Andrea Mafficini and Alessia Nottegar and Nicola Veronese and Peter Chianchiano and Brosens, {Lodewijk A.A.} and Micha{\"e}l No{\"e} and Offerhaus, {G. Johan A.} and Raluca Yonescu and Yi Ning and Giuseppe Malleo and Giulio Riva and Paola Piccoli and Ivana Cataldo and Paola Capelli and Giuseppe Zamboni and Aldo Scarpa and Wood, {Laura D.}",

note = "Funding Information: We thank Dr Ralph Hruban for helpful discussions of these data. We acknowledge the following sources of funding: NIH/NCI P50 CA62924; NIH/NIDDK K08 DK107781; Sol Goldman Pancreatic Cancer Research Center; Buffone Family Gastrointestinal Cancer Research Fund; Kaya Tuncer Career Development Award in Gastrointestinal Cancer Prevention; AGA-Bernard Lee Schwartz Foundation Research Scholar Award in Pancreatic Cancer; Sidney Kim-mel Foundation for Cancer Research Kimmel Scholar Award; AACR-Incyte Corporation Career Development Award for Pancreatic Cancer Research; Rolfe Pancreatic Cancer Foundation; Joseph C Monastra Foundation; The Gerald O Mann Charitable Foundation (Harriet and Allan Wulfstat, Trustees); Sigma Beta Sorority; Associ-azione Italiana per la Ricerca sul Cancro (12182); FP7 Health (Cam-Pac) (602783); and the Ministero della Salute (FIMP-CUP_J33G13000210001). Publisher Copyright: Copyright {\textcopyright} 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.",

year = "2017",

month = oct,

doi = "10.1002/path.4941",

language = "English (US)",

volume = "243",

pages = "148--154",

journal = "Journal of Pathology",

issn = "0022-3417",

publisher = "John Wiley and Sons Ltd",

number = "2",

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TY - JOUR

T1 - Pancreatic undifferentiated carcinoma with osteoclast-like giant cells is genetically similar to, but clinically distinct from, conventional ductal adenocarcinoma

AU - Luchini, Claudio

AU - Pea, Antonio

AU - Lionheart, Gemma

AU - Mafficini, Andrea

AU - Nottegar, Alessia

AU - Veronese, Nicola

AU - Chianchiano, Peter

AU - Brosens, Lodewijk A.A.

AU - Noë, Michaël

AU - Offerhaus, G. Johan A.

AU - Yonescu, Raluca

AU - Ning, Yi

AU - Malleo, Giuseppe

AU - Riva, Giulio

AU - Piccoli, Paola

AU - Cataldo, Ivana

AU - Capelli, Paola

AU - Zamboni, Giuseppe

AU - Scarpa, Aldo

AU - Wood, Laura D.

N1 - Funding Information: We thank Dr Ralph Hruban for helpful discussions of these data. We acknowledge the following sources of funding: NIH/NCI P50 CA62924; NIH/NIDDK K08 DK107781; Sol Goldman Pancreatic Cancer Research Center; Buffone Family Gastrointestinal Cancer Research Fund; Kaya Tuncer Career Development Award in Gastrointestinal Cancer Prevention; AGA-Bernard Lee Schwartz Foundation Research Scholar Award in Pancreatic Cancer; Sidney Kim-mel Foundation for Cancer Research Kimmel Scholar Award; AACR-Incyte Corporation Career Development Award for Pancreatic Cancer Research; Rolfe Pancreatic Cancer Foundation; Joseph C Monastra Foundation; The Gerald O Mann Charitable Foundation (Harriet and Allan Wulfstat, Trustees); Sigma Beta Sorority; Associ-azione Italiana per la Ricerca sul Cancro (12182); FP7 Health (Cam-Pac) (602783); and the Ministero della Salute (FIMP-CUP_J33G13000210001). Publisher Copyright: Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

PY - 2017/10

Y1 - 2017/10

N2 - Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UCOGC) is currently considered a morphologically and clinically distinct variant of pancreatic ductal adenocarcinoma (PDAC). In this study, we report clinical and pathological features of a series of 22 UCOGCs, including the whole exome sequencing of eight UCOGCs. We observed that 60% of the UCOGCs contained a well-defined epithelial component and that patients with pure UCOGC had a significantly better prognosis than did those with an UCOGC with an associated epithelial neoplasm. The genetic alterations in UCOGC are strikingly similar to those known to drive conventional PDAC, including activating mutations in the oncogene KRAS and inactivating mutations in the tumor suppressor genes CDKN2A, TP53, and SMAD4. These results further support the classification of UCOGC as a PDAC variant and suggest that somatic mutations are not the determinants of the unique phenotype of UCOGC.

AB - Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UCOGC) is currently considered a morphologically and clinically distinct variant of pancreatic ductal adenocarcinoma (PDAC). In this study, we report clinical and pathological features of a series of 22 UCOGCs, including the whole exome sequencing of eight UCOGCs. We observed that 60% of the UCOGCs contained a well-defined epithelial component and that patients with pure UCOGC had a significantly better prognosis than did those with an UCOGC with an associated epithelial neoplasm. The genetic alterations in UCOGC are strikingly similar to those known to drive conventional PDAC, including activating mutations in the oncogene KRAS and inactivating mutations in the tumor suppressor genes CDKN2A, TP53, and SMAD4. These results further support the classification of UCOGC as a PDAC variant and suggest that somatic mutations are not the determinants of the unique phenotype of UCOGC.

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KW - undifferentiated carcinoma with osteoclast-like giant cells

KW - whole exome sequencing

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DO - 10.1002/path.4941

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AN - SCOPUS:85028818018

SN - 0022-3417

VL - 243

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EP - 154

JO - Journal of Pathology

JF - Journal of Pathology

IS - 2

ER -

Pancreatic undifferentiated carcinoma with osteoclast-like giant cells is genetically similar to, but clinically distinct from, conventional ductal adenocarcinoma

Abstract

Keywords

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