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Digital archive of theses discussed at the University of Pisa

 

Thesis etd-12022019-104944


Thesis type
Tesi di specializzazione (5 anni)
Author
BIANCHINI, MATTEO
URN
etd-12022019-104944
Thesis title
Studio preliminare sul ruolo della proteina prionica come base biologica della neuroinvasivita dell'adenocarcinoma duttale del pancreas.
Department
PATOLOGIA CHIRURGICA, MEDICA, MOLECOLARE E DELL'AREA CRITICA
Course of study
CHIRURGIA GENERALE
Supervisors
relatore Prof. Morelli, Luca
Keywords
  • Carcinoma del pancreas; Proteina prionica
Graduation session start date
19/12/2019
Availability
Withheld
Release date
19/12/2089
Summary
Background and aim: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers. Its aggressiveness and invasiveness call for the detection of early markers. A peculiarity of PDAC is its high neurotropism, with a notable rate of perineural invasion. Prions are mainly known to be related to neurological disorders thanks to their neurotropism, but recent evidences indicate that PrP could have a role also in tumorigenesis; however, no study so far investigated in vivo the occurrence of PrP within PDAC. The aim of this study is to investigate the presence of PrP in PDAC tissues as possible marker of specific biological behavior.

Materials and methods: Between July 2018 and May 2019 samples from pancreatic tissues of 20 patients surgically treated for a suspicion of PDAC were collected. If the frozen section excluded the diagnosis of PDAC, patients were excluded. Immunohistochemistry and western blotting were used to compare the expression of PrP in PDAC and normal adjacent pancreas. We evaluated also the expression of CD155, a marker of dedifferentiation and we compared it to the staining of PrP, in order to evaluate any correlation between them.

Results: we analyzed tissue samples from 16 patients affected by PDAC (100%), with Perineural invasion in 12/16 (75%). According to the immuno-blot analysis, PrP was markedly expressed in tumor pancreatic tissues respect to controls (438,61 ± 55,41 OD vs 100 ± 16,97 OD, p<0,001). After measuring the linear staining of PrP in pancreatic ducts, we found a marked difference between PDAC compared to controls ( 125±12.51 µm vs 79,5±6,4 µm p<0.001). With immunohistochemistry we noted that the expression of PrP and CD155 exactly overlapped, highlighting the possible relationship of PrP with cancer stemness.

Conclusions: The presence of PrP might contribute to explain the biology of PDAC, in particular some peculiar characteristics such as neurotropism. Further studies are necessary to investigate the possible clinical implications.
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