Tracking the Clonal Evolution of Adenosquamous Carcinoma, a Rare Variant of Intraductal Papillary Mucinous Neoplasm of the Pancreas.
Adenosquamous carcinoma (ASC) is an uncommon variant of pancreatic neoplasm. We sought to trace the mode of tumor progression using specimens of ASC associated with intraductal papillary mucinous neoplasm (IPMN) of the pancreas. A resected specimen of the primary pancreatic ASC, developed in a 72-year-old man, was subjected to mutation profiling using amplicon-targeted sequencing and digital polymerase chain reaction. DNA was isolated from each histological compartment including noninvasive IPMN, squamous cell carcinoma (SCC), and adenocarcinoma (AC). Histologically, an IPMN with a large mural nodule was identified. The invasive tumor predominantly consisted of SCC, and a smaller AC was found around the lesion. Squamous metaplasias were sporadically distributed within benign IPMNs. Mutation alleles KRAS and GNAS were identified in all specimens of IPMN including the areas of squamous metaplasia. In addition, these mutations were found in SCC and AC. Clear transition from flat/low-papillary IPMN to SCC indicated a potent invasion front, and the SCC compartment was genetically unique, because the area has a higher frequency of mutation KRAS. The invasive tumors with distinct histological appearances shared the form of noninvasive IPMN as a common precursor, rather than de novo cancer, suggesting the significance of a genetic profiling scheme of tumors associated with IPMN.
From the *Department of Surgery, Furano Kyoukai Hospital, Furano; †Center for Clinical and Biomedical Research, Sapporo Higashi Tokushukai Hospital, Sapporo; ‡Department of Pathology, Asahikawa Medical University; §National Hospital Organization Asahikawa Medical Center; ∥Center for Advanced Research and Education, Asahikawa Medical University, Asahikawa; ¶Life Technologies Japan, Tokyo; #Department of Clinical Research, Chiba Tokushukai Hospital, Funabashi, Japan; and **Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
Suguru
S
Matsuzaka
Hidenori
H
Karasaki
Yusuke
Y
Ono
Munehiko
M
Ogata
Kensuke
K
Oikawa
Susumu
S
Tamakawa
Shin-Ichi
S
Chiba
Miho
M
Muraki
Tomoki
T
Yokochi
Hiroshi
H
Funakoshi
Toru
T
Kono
Kazuo
K
Nagashima
Yusuke
Y
Mizukami
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000235:genetics* / Q000473:pathology; D000368:Aged; D018196:Carcinoma, Adenosquamous / Q000235:genetics* / Q000473:pathology; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D002864:Chromogranins / Q000235:genetics; D060965:Clonal Evolution; D018450:Disease Progression; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics; D005787:Gene Frequency; D006801:Humans; D008297:Male; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics
D002864:Chromogranins; C117307:KRAS protein, human; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs; D016283:Proto-Oncogene Proteins p21(ras)