Cellular turnover and expression of hypoxic-inducible factor in acute acalculous and calculous cholecystitis

INTRODUCTION Epithelial corrective and destructive mechanisms have not been studied in inflammatory gallbladder disease. METHODS Epithelial apoptosis, cell proliferation and expression of hypoxia-inducible factor (HIF)-1alpha were compared in gallbladders from patients with acute acalculous cholecystitis (AAC; n = 30) and acute calculous cholecystitis (ACC; n = 21), and from patients undergoing surgery for other reasons (normal gallbladders; n = 9), which were removed during open cholecystectomy. The immunohistochemical stains included antibodies to Ki-67 (proliferation), M30 (apoptosis) and HIF-1alpha. Proliferation and apoptosis were expressed as percentages of positive cells. HIF-1alpha expression was expressed as absent, weak, or strong. RESULTS Apoptosis (median [25th to 75th percentile]) was significantly increased in AAC (1.31% [0.75% to 1.8%], P < 0.001) and ACC (1.10% [0.63% to 1.64%], P = 0.001), compared with control samples (0.20% [0.07% to 0.45%]. The proliferation rate was significantly increased in AAC (8.0% [4.0% to 17.0%], P < 0.001) and ACC (14% [7.5% to 26.5%], P = 0.001) compared with control samples (1.0% [1.0% to 3.0%]). Strong HIF-1alpha staining was observed in 57% of AAC, in 100% of ACC and in 44% of control specimens (P < 0.001). Intense HIF-1alpha expression was associated with increased cell proliferation (P = 0.002). CONCLUSION Cell proliferation and apoptosis were increased in AAC and ACC, as compared with normal gallbladders. Expression of HIF-1alpha was lower in AAC than in ACC.