The Expression And Significance Of P53, MDM2 And PCNA In Psoriasis

Objectives: Psoriasis(PS) is one of chronic and relapsing dermatogic diseases. The epidermal dynamic abnormality involves overproliferation and apoptosis acceleration of keraticytes(KCs) which is the most important feature of psoriasis. The eticlogy may involve the damage of self-equilibrium mechanism. p53 is one of anti-oncogene which has been studied most.P53 is divided into wide-type p53(wtp53) and mutant-p53 (mtp53). Wtp53 promotes cell apoptosis in normal cells which centrarole is to mediate the cell emergency reaction of DNA post traum and DNA heap ,and it also sustains genetic stability,but mtp53 has the role to suppress apoptosis. Being one of the activated production of p53 genetic transcription,MDM2 (murine double mimute 2) was activated by p53,inversely, MDM2 holds p53 activity back. Therefore both p53 and MDM2 form a self- adjusted feed-back loop to keep body physiologic function.However,MDM2 can hasten cell proliferation by interaction with other growth factors.In normal cells, MDM2 keeps a subtle balance with wtp53 remaining low level;under several damage factors such as DNA trauma, hypoxia, nucleotide deletion,p53 multiplys sharply and activates the expression of down stream target genes including its down-regulation factor MDM2;after clear up all kinds of injurying factors,both p53 and MDM2 are recoveried. The eticlogy may involve the damage of p53 self-equilibrium mechanism mediated by MDM2.By now,we havn't found any exterior and internal report of p53-MDM2 feedback loop in psoriasis.PCNA(proliferating cell nuclear antigen) has a cons- picuous periodical content diversity in proliferating cells ,which just coincides with phase change of intra-cellular DNA duplication. So PCNA is a intranuclear protein following cell proliferation and its physiological function can evaluate cellular vegetative state.It has been generally used for study of malignant tumors and some hyperplasia diseases.We detected p53,MDM2,PCNA proteins in psoriasis and Squamous Cell Carcinoma(SCC) by employing immunohisto- chemistry.On the one hand,we analysed the relationship among p53,MDM2 and keratinocyte proliferation in PS;on the other hand,we tried to study the different mechanism of action between inflo-hyperplasy disease and dermato-malignant tumor.Methods:All patients, diagnosed by clinic and histo- pathology ,were derived from the dermatology department of the Fourth Affiliated Hospital of Hebei University from October,2003 to October,2005. 45 patients, being 30 with PS,15 with SCC.The levels of p53,MDM2,PCNA expression in these patients were detected by immunohistochemical method. 15 healthy skin specimens from department of surgery were taken as controls.There were no significant difference in sexes, ages and locus of biopsy between controls and patients.Apply SPSS 11.5 statistical software handing data.Paraffin section was used by HE staining in histopathology and by histostain-SP method in immunohistochemistry.Results:(1) p53 and PCNA were stained in necleus,MDM2 was in kytoplasm or necleus. p53,MDM2 and PCNA showed negative staining or low expression in normal skin while overexpression in PS( P<0.05). The levels of p53 and MDM2 expression in SCC were significantly higher than those in PS(p<0.05). PCNA, in normal skin cells ,showed low expression, however ,it exhibited overexpression in PS and SCC ,but PCNA had no significant difference between them.(2) p53, MDM2 and PCNA showed a significant correlation in PS(P<0.05).Conclusions:(1) The level of p53 is highly expressed in PS. We may conclude that p53 protein is heaped and overexpressed,p53 is the reason of KCs proliferation.(2) The level of MDM2 in stratum spinosum and stratum granulosum are remarkly higher than in stratum basale in PS.We may presume that MDM2 protein connects with cell differention mechanism and participates cell proliferation process. (3) Both p53 and MDM2 are increased,the reason may be p53-MDM2 feedback is demolished in PS. (4) Both p53 and MDM2 increase from normal skin through PS to malignant pathological changes which suggest that the mechanism are different. (5)The expression of PCNA is significantly higher than normal which hints that the KCs stay in a state of proliferation causing uninterrupt thickenness in PS.