Prostatic atrophy: Immunohistochemical study of hypoxia induced factors

Abstract

Background: There is evidence that chronic local ischemia may be one possible etiology of prostatic atrophy (PA). Our aim was to study the expression of hypoxia induced factors in areas of PA. Design: The immunohistochemical expression of hypoxia-inducible factor-1 alpha (HIF-1) and vascular endothelial growth factor (VEGF) was studied in atrophic acini of 33 needle prostatic biopsies. Prostatic atrophy was the only diagnosis in these biopsies. For HIF-1alpha, a total of 27,158, 10,060 and 9920 nuclei were counted in atrophic acini, acini with squamous metaplasia, and acini without squamous metaplasia surrounding acute infarct, respectively. For VEGF, a total of 24,966, 9849 and 9918 nuclei were counted for the same acini. A total of 1326 nuclei were counted in acini of the needle biopsy used as negative control. The Student’s test for independent samples with significance level at 5% (p<0.05) was used to compare the mean ratio (MR) of positive nuclei over total nuclei for HIF-1 and VEGF. Results: For HIF-1, 108 (MR = 0.004), 6877 (MR = 0.68), and 6566 (MR = 0.66) nuclei were positive in atrophic acini, acini with squamous metaplasia, and acini without squamous metaplasia surrounding acute infarct, respectively. There was a highly significant difference (p<0.001) between atrophic acini and acini surrounding acute infarct. For VEGF, 139 (MR = 0.05), 5926 (MR = 0.60), and 4948 (MR = 0.50) nuclei were positive in the same acini. The difference was highly significant (p<0.001). All 1326 nuclei counted in the needle biopsy with essentially normal findings were negative for HIF-1 and VEGF. Conclusions: This study showed that prostatic atrophic acini are not on acute ischemia. However, local chronic ischemia cannot be ruled out. Experimental data showed that on chronic ischemia, the signal triggering HIF-1alpha accumulation may disappear despite continuous hypoxia suggesting that compensatory mechanisms triggered during prolonged hypoxia may be able to restore normal tissue oxygen levels.