Apoptosis and its relationship with cell proliferation, p53, Waf1p21, bcl-2 and c-myc in esophageal carcinogenesis studied with a high-risk population in northern China.

Abstract

AIM:To determine the extent of apoptosis and its possible relationship with the changes of p53, Waflp21, bcl-2, and c-myc at different stages of esophageal carcinogenesis.METHODS:Two hundred and forty-one esophageal biopsy samples from symptom-free subjects and 38 surgically resected esophageal carcinoma tissues from a high-risk population for esophageal cancer in Henan, China were used in this study.Apoptotic cells and apoptotic bodies were identified by well-established morphological criteria. The extent of apoptosis and its possible relationship with the rate of cell proliferation (PCNA) and changes of p53, Waf1p21, bcl-2,and c-myc were analyzed in samples with esophageal precancerous and cancerous lesions.RESULTS:The apoptotic cells, identified morphologically, were located in the same proliferative compartment of hyperproliferative cell population in the esophageal epithelia as the cells immunostaining-positive for p53, bcl-2, c-myc and PCNA.The apoptotic indices (total number of apoptotic cells and apoptotic bodies per mm(2) of the tissue section) were low in the normal epithelia,and increased significantly as the lesions progressed from BCH to DYS and to SCC.The extent of apoptosis correlated well with the cell proliferation indices based on PCNA. The total number of positive cells for p53 stain was much higher than that of apoptotic cells. No difference in apoptotic indices was found between p53-positive and p53-negative samples. Waf1p21-positive cells resided in cell layers were higher in number than p53 and PCNA-positive cells. The number of immunostaining positive cells for Waflp21 increased slightly from normal to BCH,but decreased in DYS and SCC. Positive staining samples for bcl-2 and c-myc increased as the lesions progressed from BCH to DYS and to SCC. No apparent correlation between apoptosis and Waf1p21, bcl-2 or c-myc expression was observed.CONCLUSION:The extent of apoptosis was low in normal esophageal epithelium and increased as the lesions progressed. The apoptotic cells were located in the same hyperproliferative cell compartment as cells immunostaining-positive for p53, bcl-2,c-myc and PCNA,but no apparent correlation between apoptosis and these parameters was observed,possibly due to the complexities of molecular changes in esophageal carcinogenesis.