title: An investigation of the role of the systemic and local inflammatory response in patients undergoing resection for renal cell carcinoma
Creators: name: Lamb, Gavin W.A.
Publisher: name: University of Glasgow
Year: 2008
Subjects: subject: Immunology, oncology, kidneys, cancer.

description: Although renal cell carcinoma accounts for only 2% of all cancers it is responsible for 12% of all cancer deaths making it a particularly lethal malignancy. Over the last 50 years there has been an increased incidence in all stages of disease with the greatest rise observed in localised lesions found incidentally due to increased used of radiological imaging. The mainstay of treatment for the 60% of patients presenting with only localised disease is surgery however, despite aggressive surgical management 30% of patients with no evidence of metastases at the time of surgery will subsequently develop metastases. The median survival of patients either presenting or developing metastatic disease is 8.5 months even in those who are suitable for immunotherapy. Currently staging and consequently the prognosis of patients with renal cancer is based on macroscopic tumour characteristics and the presence or absence of lymph node and distant metastases as defined by the American Joint Committee on Cancer TNM staging system. Stage alone has been shown to be inadequate in predicting outcome and combination with grade and histological subtype has been shown to improve prognostication in patients with renal cancer. Additionally patient factors are thought to contribute to patients overall cancer specific survival including the presence of cachexia and poor performance status. The reasons for these factors influencing survival are not clear but their potential relationship with the systemic inflammatory response, as evidenced by raised circulating concentrations of C-reactive protein is thought to be significant. Previous work has shown that elevated C-reactive protein signifying a systemic inflammatory response is of independent prognostic value in patients undergoing potentially curative resection for a variety of common solid tumours. In chapter 2 we examined patients undergoing potentially curative nephrectomy for renal cancer, the presence of a systemic inflammatory response has been tested for its prognostic significance against the UISS (UCLA Integrated Staging System) an internationally validated prognostic algorithm incorporating stage, grade and performance status. In this study of 100 patients a raised C-reactive protein was found to be an independent prognostic factor for cancer specific survival on both univariate and multivariate analysis. In chapter 3 patients undergoing nephrectomy for renal cancer were examined for CD4+ and CD8+ tumour lymphocytic infiltrate, interleukin-6 receptor expression, cyclo-oxygenase-2 expression as well as concentrations of circulating C-reactive protein with relation to cancer specific survival. Both elevated C-reactive protein and increased numbers of CD4+ lymphocytic infiltrate were associated with poorer cancer specific survival. A positive relationship was also demonstrated between T-lymphocytic infiltrate and C-reactive protein and were both significantly associated with increased grade of tumour suggesting an association with more aggressive tumour biology. Cyclo-oxygenase 2 and interleukin-6 receptor expression were found to be independent of tumour stage, grade, lymphocytic infiltrate and not related to cancer specific survival. In conclusion the work presented in this thesis suggests that both the presence of a systemic or a local inflammatory response are negative prognostic factors in patients undergoing nephrectomy for renal cancer. Systemic C-reactive protein and tumour lymphocytic infiltrate are significantly associated with each other. Tumour expression of cyclo-oxygenase-2 and interleukin-6 receptor are independent of circulating C-reactive protein and local lymphocytic infiltrate and are therefore the basis for the link between the local and systemic inflammation observed in renal cancer is unclear and warrants further study. (Abstract shortened by ProQuest.).