Pre-operative radiotherapy for patients with locally advanced rectal carcinoma has been shown to improve survival rates and local tumour control. The ability to identify tumours most likely to undergo a complete or partial response would improve the selection of patients for radiotherapy and potentially modify post-treatment planning. The aim of this study was to develop a multi-marker model of tumour response to pre-operative high-dose rate endorectal brachytherapy (HDREB). Immunohistochemistry (IHC) for p53, Bcl-2, VEGF, APAF-1 and EGFR was carried out on 104 pre-treatment rectal tumour biopsies from patients undergoing a pre-operative HDREB protocol. Immunoreactivity was scored by at least three pathologists using a semi-quantitative scoring method. The reproducibility of the scoring system was evaluated. Receiver operating characteristic curve (ROC) analysis was performed for each protein to determine clinically relevant cutoff scores for defining tumour positivity. Multivariate logistic regression analysis was carried out to identify independent predictive factors of tumour response. Both the semi-quantitative scoring system and ROC curve analysis were found to be reproducible. In addition, the combined analysis of VEGF and EGFR was highly predictive of complete pathologic response to radiotherapy. EGFR was found to independently predict complete or partial tumour regression but only with low sensitivity and specificity. A large-scale prospective study is necessary to confirm these findings. Moreover, the novel methodology proposed and validated in this study to assess immunoreactivity could significantly enhance the value of IHC findings in colorectal cancer as well as other tumour types.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.103189 |
| Date | January 2007 |
| Creators | Zlobec, Inti. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Pathology.) |
| Rights | © Inti Zlobec, 2007 |
| Relation | alephsysno: 002598582, proquestno: AAINR32393, Theses scanned by UMI/ProQuest. |
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