Host Immune Response in Staging and Recurrence of Urothelial Bladder Carcinoma

Abstract

The present study was undertaken to identify host immune factors and a signature immune profile of bladder cancer in tumour tissue, serum and urine associated with recurrence and progression. The tumour microenvironment is constituted by mononuclear inflammatory cells, newlinepredominantly NK cells and macrophages. The cells expressing the T-cell markers, CD4/CD8 and the transcription factors of Th1/Th2 lineage i.e., TBX21/GATA3 were much less in number. TBX21 expression in inflammatory cells was not found associated with either grade or stage but GATA3 was found to be significantly higher in the inflammatory cells in low grade cases (p=0.008). The expression of the pro-inflammatory marker, cyclo-oxygenase enzyme 2 (COX2) gene was found to be ubiquitous in inflammatory cells (93.5% cases) and was not associated with stage or grade. TBX21, GATA3 and COX2 were also expressed in tumour cells in 35.4%, 47.4% and 37.2% cases respectively. TBX21 expression was found to be significantly higher in muscle-invasive cases (p=0.026) while that of COX2 was associated with recurrence and poor recurrence free survival (RFS). The role of TBX21 expression in tumour cells has been associated with a bad prognosis in breast cancer and COX2 tumour cell expression has been previously reported to have a role in invasion and metastasis. Hence a signature profile of loss of GATA3 in inflammatory cells and expression of TBX21 and COX2 in tumour cells appears to indicate bad prognosis and poor survival in urothelial cancer patients. COX2 inhibitors such as NSAIDs (non-steroidal anti-inflammatory drugs) and coxibs may play a role in treatment of COX2 positive tumours. This profile may be adopted for screening and for guiding the management of these patients. newlineGene expression