[Gastric cancer and tumor growth regulation. Study of cell proliferation markers and protein complex p53/p21WAF1/CIP1/mdm-2].
BACKGROUND
p53/p21WAF1/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 history.


OBJECTIVE
To study the relationship between the immunohistochemical expression of p53/p21WAF1/CIP1 and mdm-2 and cell proliferation in gastric cancer.


METHODS
Fifty one gastrectomy specimens with gastric cancer were studied using immunohistochemistry for p53/p21WAF1/CIP1 and mdm-2. Cell proliferation was determined by immunolabelling with PCNA and Ki67 antigens. Mitosis figures were counted in 10 high power microscopic fields.


RESULTS
Patients from whom gastric cancer specimens were obtained had a mean age of 59.3 years. Ki67 and mitosis counting showed the highest correlation index with proliferation indexes studied. No correlation was found between the expression of protein complex p53/p21WAF1/CIP1 and mdm-2 and morphological characteristics of gastric tumors. Mdm-2 protein overexpression was the only marker that showed an independent correlation with cell proliferation. Moreover, mdm-2 positive tumors showed the highest proliferation indexes when p53 was not immunohistochemically over-expressed, 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 overexpression could play a major role in gastric carcinogenesis.
Villaseca
M
M
Departamento de Ciencias Preclínicas, Facultad de Medicina, Universidad de La Frontera, Temuco, Chile. mvilla@ufro.cl
Araya
J C
JC
Roa
I
I
Roa
J C
JC
D014408:Biomarkers, Tumor / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D008938:Mitosis; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2