Kawesha, Anthony (2017). Prognostic molecular markers in resected ductal pancreatic carcinoma. University of Birmingham. M.D.
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Kawesha17MD.pdf
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Abstract
Previous studies of molecular prognostic markers following resection for exocrine pancreatic cancer have produced conflicting results. The aim of this study was to undertake a comprehensive analysis of potentially useful markers in a large multicentre patient population and compare these markers with standard pathological prognostic variables. Formalin fixed, paraffin-embedded specimens of pancreatic ductal adenocarcinoma were analysed from 157 patients (100 men and 57 women with a median [range] age of 60 [33-77] years) who had undergone pancreatectomy. Immunhistochemistry was used to detect expression of p16\(^{INK4}\), p53, p21\(^{WAF1}\), cyclin D1, c-erbB-2 and c-erbB-3. In a selected number of p53 positive and negative staining cases, mutational analysis was undertaken using DNA obtained from microdissected specimens. Mutations in codons 12 and 13 of the K-ras oncogene were detected by SSCP and sequencing following DNA extraction and amplification by PCR. The median [range] survival post-resection was 12.5 [3-83] months. Abnormalities of p16\(^{INK4}\), p53, p21\(^{WAF1}\), cyclin D1, c-erbB-2 and c-erbB-3 expression were found in 87%, 41%, 75%, 72%, 33% and 57% of cases, respectively. There was no significant correlation between expression of any of these markers and patient survival. K-ras mutations were found in 73 (75%) out of 97% cases with amplifiable DNA. The presence of K-ras mutation alone did not correlate with survival, but there were significant differences in survival according to the type of K-ras mutation (p=0.0007). Reduced survival was found in patients with GaT, cGT and GcT K-ras mutations compared to GtT, aGT and GaC mutations. In conclusion survival was associated with the type of K-ras mutation but not the expression of p16\(^{INK4}\), p53, p21\(^{WAF1}\), cyclinD1, c-erbB-2 and c-erbB3.
Type of Work: | Thesis (Higher Doctorates > M.D.) | ||||||||||||
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Award Type: | Higher Doctorates > M.D. | ||||||||||||
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College/Faculty: | Colleges (2008 onwards) > College of Medical & Dental Sciences | ||||||||||||
School or Department: | School of Clinical and Experiment Medicine, Department of Medicine and Medical Education | ||||||||||||
Funders: | None/not applicable | ||||||||||||
Subjects: | Q Science > QH Natural history > QH426 Genetics R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) |
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URI: | http://etheses.bham.ac.uk/id/eprint/7596 |
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