Tyrosine Kinase Growth Factors in Gastric Cancer

Lannigan, Alison Kerr (2000) Tyrosine Kinase Growth Factors in Gastric Cancer. MD thesis, University of Glasgow.

Abstract

In the West of Scotland in the last thirty years there has been a definite decrease in the incidence and mortality from gastric cancer but the survival of patients who develop adenocarcinoma of the stomach remains poor. This thesis is introduced by an audit of gastric cancer in a single centre over a period of twenty years. This aims to describe changes in the presentation, diagnosis and management of the condition during the period of study. Overall, despite improvements in investigation the disease still presents at an advanced stage and rates of curative resection are low. Advances in surgical technique and post-operative care have not improved long term survival with little significant additional benefit from current adjuvent medical therapy. The tyrosine kinase growth factor receptors have been investigated in a number of human cancers including breast, colon, ovarian and squamous carcinoma. In gastric cancer, the level of expression and prognostic value of EGFr and c-erbB-2 have been reported with some considerable variation using standard immunohistochemistry. To assess the use of growth factors as tumour markers or potential therapeutic targets, reliable quantitative and reproducible measurements of expression must be established. This study reports the quantitative expression of EGFr and c-erbB-2 using radioimmunohistochemistry (RIHC) and compares the results with expression using conventional immunohistochemistry (IHC). The correlation of established clinico- pathological factors with EGFr, c-erbB-2 and the gene amplification of c-erbB-2 using fluorescence in situ hybridisation is investigated. In both EGFr and c-erbB-2 expression there is good overall correlation analysis using RIHC and IHC (p<0.0005) but the separation of results is significantly better with RIHC particularly in the higher expressing tumours. In comparing tumour to mucosal samples, 22.4% of tumours expressed c-erbB-2 at a higher level, using RIHC and 43.3% with IHC. EGFr was expressed in 22.4% of cases more than the mucosal range with RIHC and 41. 8% with IHC. There was no correlation of EGFr and c-erb-2 (r2 = 0.004, p = 0.594). In this study there is significant correlation of c-erbB-2 with well and moderately well differentiated tumours (p=0.008) and no serosal involvement (p=0.066). EGFr in this study also appears to correlate with well and moderately well differentiated tumours (p=0.079). There was no correlation between EGFr, c-erbB-2 and patient survival. This thesis has demonstrated IGF-I induced cellular proliferation with a dose dependent inhibition by the tyrophostin RG13022. IGF-I is found to be a less potent stimulator of the MAP kinase pathway than EGF and RG13022 is less able to inhibit this pathway.

• Item Type: Thesis (MD)
• Qualification Level: Doctoral
• Additional Information: Adviser: Colin McArdle
• Keywords: Medicine, Oncology
• Date of Award: 2000
• Depositing User: Enlighten Team
• Unique ID: glathesis:2000-76037
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 19 Dec 2019 09:15
• Last Modified: 19 Dec 2019 09:15
• URI: https://theses.gla.ac.uk/id/eprint/76037