Significance Of P16, P27, CyclinD1, CDK4 And Rb Expression In Gastric Carcinoma And Precancerous Lesion

bjective: To evaluate the roles of the Gl restriction point-regulating proteins pi6,p27, cyclinDl, CDK4 and Rb in the genesis and progression of gastric carcinoma, andtheir relationship to each other as well as to the biological behavior of gastriccarcinoma.Methods: The immunohistochemical method was used to detect the expression ofp16, p27, cyclinDl, CDK4 and Rb in superficial gastritis, atrophic gastritis, intestinalmetaplasia, dysplasia and gastric carcinoma specimens; the levels of these proteins intissues with different types of lesion and their correlation with clinicopathologicalparameters of gastric carcinoma were analyzed.Results: (1)The expression of p!6 showed no significant difference among differenttypes of lesion, and it was not correlated with any clinicopathological parameter ofgastric carcinoma (P>0.05).(2)The expression level of p27 in gastric carcinoma tissues was significantly lowerthan that in other tissues (P<0.01), and it was significantly correlated with depth ofinvasion, lymph node metastasis, distant metastasis and TNM stage of gastriccarcinoma (P<0.01), for it was more lower in gastric carcinomas with serosalinfiltration, lymph node metastasis, distant metastasis, or late TNM stage than thosewithout.(3)The expression level of cyclinDl in dysplasias was significantly higher than that inother lesions(P<0.01). There is no significant correlation between cyclinDlexpression and any clinicopathological parameter of gastric carcinoma (P>0.05).(4)The expression level of CDK4 in dyspalsias and gastric carcinomas wassignificantly higher than that in other lesions (PO.01). There is no significantcorrelation between CDK4 expression and any clinicopathological parameter ofgastric carcinoma (P>0.05).(5)The expression of Rb was consistently high in benign and malignant lesions, and itwas not correlated with any clinicopathological parameter of gastriccarcinoma (PXX05).(6)There was a negative correlation between the expression of p!6 and cyclinDl, but apositive correlation between the expression of p27 and cyclinDl (P<0.01).Conclusion: Deregulation of the Gl restriction point is highly related to the genesisand progression of gastric carcinoma. Aberrant expression of some importantregulators of the restriction point including pi6, p27, cyclinDl, CDK4 and Rb wereobserved in gastric carcinomas and precancerous lesions, indicating:(1)Loss of p16 expression may be involved in the genesis of some gastric carcinomas.(2)Overexpression of cyclinDl may be an early event in gastric carcinogenesis.(3) Overexpression of CDK4 plays an important role in the pathogenesis andprogression of gastric carcinoma.(4)Rb protein may be involved in the pathogenesis and progression of gastriccarcinoma mainly via its functional inactivation.(5)Aberrant expression of p27 is an important molecular mechanism involved in thepathogenesis and progression of gastric carcinoma. The assessment of p27 expressionmay prove valuable in distinguishing between benign and malignant lesions, andevaluating the malignant degree as well as prognosis of gastric carcinoma.(6)There is a negative feedback regulatory loop between pi6 and cyclinDl expressionas well as a positive feedback loop between p27 and cyclinDl expression.