Immunohistochemical estimation of hypoxia in human obstructed bladder and correlation with clinical variables

OBJECTIVE To investigate the tissue distribution of ischaemia in human detrusor in patients with bladder outlet obstruction (BOO) and to correlate the results with clinical variables, as clinical BOO is a common problem in ageing men and ischaemia might be important in detrusor dysfunction. PATIENTS AND METHODS From September 2004 to October 2006, 70 patients were recruited, comprising 60 scheduled for surgery to treat benign prostatic hyperplasia (the study group) and 10 as controls. Detrusor tissue was retrieved and stained for hypoxia-inducible factor (HIF)-1 alpha, a cellular marker of hypoxia. RESULTS The mean (SD) total number of cells immunoreactive to HIF-1 alpha in the study group was 93.3 (48.09), and in the specimens from the control group only few rare cells showed weak immunoreactivity to HIF-1 alpha (0-2). Positive cells were in different proportions between muscle bundles and submucosa, expressed mainly in stromal cells. The urothelium and detrusor muscle showed no immunoreactivity to HIF-1 alpha. There was strong immunoreactivity in patients with prolonged BOO (< 10 years), declining thereafter, and in those patients with urinary retention. CONCLUSIONS The urothelium and detrusor seem to be more resistant to hypoxic stress, while stromal cells perceive low oxygen tension. The bladder response to chronic hypoxia through HIF-1 alpha expression is limited in time and might depend on the functional status of the detrusor.