Objective To investigate the expression of cell division regulators p16, Rb and cyclin D1 in human early gasric carcinoma tissues and their role in tumor transformation and the correlation among p16, Rb and cyclin D1. MethodsA comparative study was carried out by using immuno-histochemical techniques between the paracarcinomatous intestinal metaplasia of 39 cases of early gatric carcinoma and the non-carcinomatous gastric mucosal intestinal metaplasia tissues of 34 cases.ResultsOver expression of cyclin D1 was determined in 33/39 carcinomatous samples(84.6%) and also in para-carcinomatous intestinal metaplasia tissues. p16 was undetectable in 12 of 39 samples. Interestingly, 15 of 26 Rb positive cancers had no or low p16,while 9 Rb negative cancers showed high levels of p16.Conclusion The over expression of cyclin D1 may be a common molecular abnormality and an early molecular event in early gastric carcinoma. Cyclin D1 over expression and Rb inactivation can co-exist in early gastric carcinoma. However, there is a reciprocity between Rb inactivation and p16 expression in early gastric carcinoma. Thus, abnormality in the negative feedback regulatory pathway of cyclin D1,Rb and p16 may be related to the tumorigenesis in early gastric carcinoma.