Gastric cancer and tumor growth regulation. Study of cell proliferation markers and protein complex p53/p21(WAF1/CIP1)/mdm-2

Background: p53/p21(WAF1/CIP1) and mdm-2 proteins play an important role in cell cycle regulation. The study of the pathogenesis of gastric cancer is important to understand how these tumors progress during their natural hist ory. Aim: To study the relationship between the immunohistochemical express ion of p53/p21(WAF1/CIP1) and mdm-2 and cell proliferation in gastric cance r. Material and methods: Fifty one gastrectomy specimens with gastric cance r were studied using immunohistochemistry for p53/p21(WAF1/CIP1) and mdm-2. Cell proliferation was determined by immunolabelling with PCNA and Ki67 an tigens. Mitosis figures were counted in 10 high power microscopic fields. R esults: Patients from whom gastric cancer specimens were obtained had a mea n age of 59.3 years. Ki67 and mitosis counting showed the highest correlati on index with proliferation indexes studied. No correlation was found betwe en the expression of protein complex p53/p21(WAF1/CIP1) and mdm-2 and morph ological characteristics of gastric tumors. Mdm-2 protein overexpression wa s the only marker that showed an independent correlation with cell prolifer ation. Moreover, mdm-2 positive tumors showed the highest proliferation ind exes when p53 was not immunohistochemically overexpressed, as determined by PCNA labelling index. Conclusions: In gastric cancer, a direct correlation between mdm-2 overexpression and cell proliferation was observed. Moreover , the fact that mdm-2 positive tumors showed the highest cell proliferation when p53 was not overexpressed, entitles us to hypothesize that mdm-2 over expression could play a major role in gastric carcinogenesis.