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- Title
Fhit down-regulation is an early event in pancreatic carcinogenesis.
- Authors
Fassan, Matteo; Rusev, Borislav; Corbo, Vincenzo; Gasparini, Pierluigi; Luchini, Claudio; Vicentini, Caterina; Mafficini, Andrea; Paiella, Salvatore; Salvia, Roberto; Cataldo, Ivana; Scarpa, Aldo; Huebner, Kay
- Abstract
Aberrant Fhit expression characterizes a large proportion of primary pancreatic ductal adenocarcinomas (PDACs), but fragmentary information is available on Fhit expression during the phenotypic changes of pancreatic ductal epithelium during multistep transformation. We assessed Fhit expression by immunohistochemistry in two different multistep pancreatic carcinogenic processes: pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasia (IPMN). We considered 105 surgically treated PDACs/IPMNs and selected 30 samples of non-neoplastic pancreatic parenchyma, 50 PanIN lesions, 30 IPMNs, 15 IPMNs with associated invasive carcinoma, and 60 adenocarcinomas. Normal pancreatic ducts and surrounding acinar cells consistently showed moderate to strong Fhit immunoreactivity. Significant down-regulation of Fhit expression was observed in association with increasing severity of dysplastia/neoplastia in both carcinogenic processes. This was further confirmed by studying multiple lesions obtained from the same surgical specimen. Of 60 PDACs, only 14 showed Fhit expression comparable to normal pancreatic ductal epithelium, while the remainder (77%) showed clearly negative or reduced Fhit expression. This study demonstrates that Fhit down-regulation is an early event in both multistep carcinogenic processes leading to PDAC.
- Subjects
PANCREATIC cancer genetics; DOWNREGULATION; ADENOCARCINOMA; CARCINOGENESIS; PANCREATIC intraepithelial neoplasia; GENETICS; BIOCHEMISTRY; HYDROLASES; IMMUNOHISTOCHEMISTRY; PHENOMENOLOGY; PANCREATIC tumors; PROTEINS; RESEARCH funding; RETROSPECTIVE studies; CARCINOMA in situ; DUCTAL carcinoma; NEOPLASTIC cell transformation; METABOLISM
- Publication
Virchows Archiv: European Journal of Pathology, 2017, Vol 470, Issue 6, p647
- ISSN
0945-6317
- Publication type
journal article
- DOI
10.1007/s00428-017-2105-3