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Aneuploidy in pancreatic intraepithelial neoplasia. / Alina Raluca Morhan

Swansea University Author: Alina Raluca Morhan

Abstract

Pancreatic ductal adenocarcinoma has one of the most unfavourable prognoses and survival patterns. Pancreatic intraepithelial ductal neoplasias (PanINs) 1-3 are microscopic precursors which display genetic and epigenetic changes leading to adenocarcinoma. We investigated the chromosomal numeric chan...

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Published: 2015
Institution: Swansea University
Degree level: Doctoral
Degree name: Ph.D
URI: https://cronfa.swan.ac.uk/Record/cronfa42775
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last_indexed 2019-10-21T16:48:26Z
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spelling 2018-08-29T15:00:31.8763196 v2 42775 2018-08-02 Aneuploidy in pancreatic intraepithelial neoplasia. 27cb017db8124b622037499feb8eca21 NULL Alina Raluca Morhan Alina Raluca Morhan true true 2018-08-02 Pancreatic ductal adenocarcinoma has one of the most unfavourable prognoses and survival patterns. Pancreatic intraepithelial ductal neoplasias (PanINs) 1-3 are microscopic precursors which display genetic and epigenetic changes leading to adenocarcinoma. We investigated the chromosomal numeric changes for chromosomes 1, 6, 9 and 18 using fluorescence in situ hybridization in the progressing intraepithelial neoplasias and the corresponding tumours. We also assessed the protein levels for mitotic checkpoint proteins Mad2 and BubRl using immunohistochemistry and applied correlation models to derive potential significant correlations to chromosome numeric anomalies and clinicopathological parameters. The results revealed that, for the chromosomes included in the study, the average numeric anomalies (aneuploidy) increases with the advancing histological stage. Moreover, the extra copy anomalies (amplifications) were significantly higher in the final precancerous stage (PanIN 3) and/or the cancer stage (p-value<0.05). The protein levels for Mad2 and BubRl did not show a direct correlation to the aneuploidy levels but that could be due to the diversity of the individual tumour makeup and the limited specimens included in the analysis. In the current trend towards personalized genetic therapy for aggressive tumours, the aneuploidy levels and the mitotic checkpoint protein levels could potentially be incorporated in a panel of biomarkers used to predict prognoses and survival patterns. E-Thesis Medicine. 31 12 2015 2015-12-31 COLLEGE NANME Swansea University Medical School COLLEGE CODE Swansea University Doctoral Ph.D 2018-08-29T15:00:31.8763196 2018-08-02T16:24:30.4609976 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Alina Raluca Morhan NULL 1 0042775-02082018162520.pdf 10807544.pdf 2018-08-02T16:25:20.9730000 Output 11433439 application/pdf E-Thesis true 2018-08-02T16:25:20.9730000 false
title Aneuploidy in pancreatic intraepithelial neoplasia.
spellingShingle Aneuploidy in pancreatic intraepithelial neoplasia.
Alina Raluca Morhan
title_short Aneuploidy in pancreatic intraepithelial neoplasia.
title_full Aneuploidy in pancreatic intraepithelial neoplasia.
title_fullStr Aneuploidy in pancreatic intraepithelial neoplasia.
title_full_unstemmed Aneuploidy in pancreatic intraepithelial neoplasia.
title_sort Aneuploidy in pancreatic intraepithelial neoplasia.
author_id_str_mv 27cb017db8124b622037499feb8eca21
author_id_fullname_str_mv 27cb017db8124b622037499feb8eca21_***_Alina Raluca Morhan
author Alina Raluca Morhan
author2 Alina Raluca Morhan
format E-Thesis
publishDate 2015
institution Swansea University
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
active_str 0
description Pancreatic ductal adenocarcinoma has one of the most unfavourable prognoses and survival patterns. Pancreatic intraepithelial ductal neoplasias (PanINs) 1-3 are microscopic precursors which display genetic and epigenetic changes leading to adenocarcinoma. We investigated the chromosomal numeric changes for chromosomes 1, 6, 9 and 18 using fluorescence in situ hybridization in the progressing intraepithelial neoplasias and the corresponding tumours. We also assessed the protein levels for mitotic checkpoint proteins Mad2 and BubRl using immunohistochemistry and applied correlation models to derive potential significant correlations to chromosome numeric anomalies and clinicopathological parameters. The results revealed that, for the chromosomes included in the study, the average numeric anomalies (aneuploidy) increases with the advancing histological stage. Moreover, the extra copy anomalies (amplifications) were significantly higher in the final precancerous stage (PanIN 3) and/or the cancer stage (p-value<0.05). The protein levels for Mad2 and BubRl did not show a direct correlation to the aneuploidy levels but that could be due to the diversity of the individual tumour makeup and the limited specimens included in the analysis. In the current trend towards personalized genetic therapy for aggressive tumours, the aneuploidy levels and the mitotic checkpoint protein levels could potentially be incorporated in a panel of biomarkers used to predict prognoses and survival patterns.
published_date 2015-12-31T03:53:37Z
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score 11.021648

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