A Study On Expression Of P21,survivin And P16 In Human Oral Lichen Planus And Oral Squamous Cell Carcinoma

BackgroundOral Lichen Planus(oral lichen planus,OLP) is a chronic inflammatory disease with abnormal keratinization which occurres in the superficial buccal mucous membrane,and appeares in skin and mucous membrane alone or simultaneously.More women than men can get the disease.In addition,OLP is precancerous lesions,and the canceration rate is 0.4%--12.3%.Oral squamous cell carcinoma(oral squamous cell carcinoma,OSCC) is the most common oral malignant tumour.And it is epithelial tumors which occurres through a dynamic process, "normal cellâ†'precancerous lesionsâ†'carcinoma",which is controlled by the gene. Gene ras is one of the most mutable genes in human cells,and ras oncogene plays an important role in oral cancer.Oncogene gene has been activated and mutated before the tumor morphology significant change.Each ras gene encodes a GMP binding protein which is highly syngeneic.Its molecular weight is 21kb,and so it is called protein P21.Ras gene family include three kinds of cancerous genes mainly,H-ras,K-ras and N-ras,which have similar structure. Gene survivin is a new member of inhibitor of apoptosis protein family,and it can cause tumor cell to proliferate and avoid apoptosis by expressing highly.Besides,it plays a part in the process of cell mitosis,and owns a dual role of inhibiting apoptosis and regulating cell proliferation.Gene survivin can be expressed in embryonal tissue,but not in end mature differentiated tissue,and highly expressed in most malignant tumour.Protein P16 is a cyclin-dependent kinase inhibitors (CDK-inhibitors).And abnormal P16 gene can cause tumour.Reports on research about the expression relations of P21 protein,survivin protein and P16 protein in oral precancerous lesions and oral squamous cell carcinoma in and abroad are few,so their possible role in oral tumor development remains unclear.ObjectivesTo study the expression and significance of P21,survivin,P16 gene in normal oral mucosa,Oral Lichen Planus(OLP) and oral squamous cell carcinoma(OSCC), and thus provide a theoretical basis for detecting OLP carcinomatous change.Materials and methodsAll the specimen were selected from the paraffin block kept in Pathology Department of the First Affiliated Hospital of Zhengzhou University from 1998 to 2007 and tissue which is cut off during surgery or for biopsy in stomatology(fixed by 10%formalin,and paraffin-embedded).Selected 26 cases of normal oral mucosa (all were from the edge of mucosa cut from mucous gland cyst),40 cases of erosive oral lichen planus,and 40 cases of oral squamous cell carcinoma,of which 13 cases were in gradeâ… ,14 cases in gradeâ…¡,and 13 cases in gradeâ…¢.And 3 cases were oral lichen Planus canceration.26 cases of normal oral mucosa were taken as a control group.S-P immunohistochemical staining was used to detect P21,survivin and P16 protein,and calculated the positive cells and the rate of positive cells,and then made statistical analysis on each set of data using rank sum test and spearman's analysis,takingα=0.05 as a test level.Results1.The positive rate of P21 in normal oral mucosa was 13.04%(3/26),in erosive OLP was 35.00%(14/40),and in oral squamous cell carcinoma was 60.00%(24/40). Contrasted with normal control group,the count of positive cell of squamous cell carcinoma group and erosive oral lichen planus group both had significant differrence (P＜0.05);Contracting squamous cell carcinomaâ… ,â…¡-class group with erosive oral lichen planus group,the positive cell count had significant difference(P＜0.05). However,the difference between squamous cell carcinoma gradeâ…¢group and erosive oral lichen planus group was not significant(P＞0.05).And so,P21 protein plays an important role in the change from OLP to OSCC,and in the staging of OSCC and prognosis.2.The expression rate of survivin protein in normal oral mucosa was very low, accounting for 3.8 percent(1/26),and in erosive OLP tissu was 30%(12/40),and so there was statistical significance between the two groups(P＜0.05).The positive expression rate of survivin protein in OSCC tissue from 22 patients(5cases in gradeâ… ,10cases in gradeâ…¡,7cases in gradeâ…¢) was 55%(22/40).So the expression of survivin protein in OSCC was higher than normal oral mucosa(P＜0.05),and the positive cell count in erosive OLP and squamous cell carcinoma was significantly different(P＜0.05).But there was no statistical significance between squamous cell carcinoma gradeâ… and erosive OLP(P＞0.05).While there was statistical significance among squamous cell carcinomaâ…¡,â…¢and erosive OLP groups(P＜0.05).The results suggested that survivin play an important role in the development of OLP and OSCC,but it may not be as a major factor in the process from erosive OLP to OSCC.3.The expression rate of P16 protein in normal oral mucosa,erosive OLP and OSCC was 84.62%(22/26),52.50%(21/40) and 22.50%(9 / 40).So there was statistical significance in the expression of P16 protein among the 3groups(P＜0.05),and the expression intensity of P16 protein reduced gradually.It was suggested that low expression of P16 protein may be one of the reasons for tumor.Conclusions1.There was a rise in the expression of P21 protein in OLP and OSCC,which suggested that P21 protein may appear in oral mucosa precancer,and so it can be used as an important indicator in detecting cancer.2.There was a rise in the expression of survivin in normal oral mucosa,erosive OLP and OSCC with the increaseing degree of abnormity in tissue.And it was indicated that survivin protein play an important role in the emergence and development of OLP and OSCC,and in the process from OLP to OSCC.3.There was a decrease in the expression of P16 protein expression with the with the increaseing degree of abnormity in tissue,and so P16 protein played an important part in the canceration of oral mucosa precancerous lesion.4.There was close positive correlativity among the formation of oral squamous cell carcinoma with the high expression of P21 protein and survivin protein.5.There was obvious relativity between P21 protein and P16protein,and with the increase of P21 protein,P16 protein decreased gradually in the development of oral mucosa cancer.6.There was obvious negative relativity between the the high expression of survivin protein and low expression of P16 protein in the process from the normal oral mucosa,OLP to OSCC.