Format

Send to

Choose Destination
Virchows Arch. 2017 Jun;470(6):647-653. doi: 10.1007/s00428-017-2105-3. Epub 2017 Mar 13.

Fhit down-regulation is an early event in pancreatic carcinogenesis.

Author information

1
ARC-NET Research Centre, Department of Diagnostics and Public Health, University of Verona, Verona, Italy. matteo.fassan@unipd.it.
2
Department of Medicine (DIMED), Surgical Pathology Unit, University of Padua, Via Gabelli 61, 35121, Padua, Italy. matteo.fassan@unipd.it.
3
ARC-NET Research Centre, Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
4
Comprehensive Cancer Center, Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH, USA.
5
Department of Diagnostics and Public Health, Surgical Pathology Unit, University and Hospital Trust of Verona, Verona, Italy.
6
Department of Pathology, Santa Chiara Hospital, Trento, Italy.
7
Department of Surgery, Unit of General Surgery B, University and Hospital Trust of Verona, Verona, Italy.

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.

KEYWORDS:

Biomarkers; Carcinogenesis; FHIT; Pancreatic cancer

PMID:
28289900
PMCID:
PMC5568551
DOI:
10.1007/s00428-017-2105-3
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Springer Icon for PubMed Central
Loading ...
Support Center