Open AccessMetachronous pancreatic cancer originating from disseminated founder pancreatic intraductal neoplasias (PanINs)
Author(s) -
Imai Koji,
Karasaki Hidenori,
Ono Yusuke,
Sasajima Junpei,
Chiba Shinichi,
Funakoshi Hiroshi,
Muraki Miho,
Hanaoka Hideki,
Furukawa Takahisa,
Furukawa Hiroyuki,
Kono Toru,
Nagashima Kazuo,
Mizukami Yusuke
Publication year - 2015
Publication title -
the journal of pathology: clinical research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.849
H-Index - 21
ISSN - 2056-4538
DOI - 10.1002/cjp2.8
Subject(s) - kras , pancreas , pancreatic cancer , pancreatic intraepithelial neoplasia , adenocarcinoma , somatic evolution in cancer , biology , pathology , pancreatic duct , somatic cell , cancer research , pancreatic ductal adenocarcinoma , medicine , cancer , gene , genetics , colorectal cancer
Clonal populations originated from benign‐looking ‘founder cells' may spread widely within pancreas instead of being localized in situ before frank pancreatic ductal adenocarcinoma (PDA) can be detected. Metachronous PDA is not common event, and we here sought to define potent origin of multiple PDAs developed in a woman using advanced genetics technologies. Curative resection of pancreatic head tumour was performed; however, ‘recurrent' lesions in the remnant pancreas were found 3.5 years later and total pancreatectomy was subsequently performed. The metachronous lesions were morphologically similar to the primary PDA. Using a next‐generation sequencing and digital PCR, all three PDAs were shown to possess rare somatic mutations in KRAS (p.T58I & p.Q61H). Curiously, identical KRAS mutations were found in low‐grade ‘intraepithelial' lesions, which localized in normal area of the pancreas and one of them possessed p53 mutation, which was also found in the PDAs. The footprint of the tumour evolution marked by mutational profiling supports a human correlate to the mouse models of ‘dissemination' occurring at the earliest stages of pancreatic neoplasia.