The Expression And Significance Of P63, P15 And Mdm2 In Human Oral Lichen Planus And Human Squamous Cell Carcinoma

BackgroundAs a common chronic inflammation of oral mucosa, Oral lichen planus (OLP), which was classified as a precancerous condition by WHO, has a significant risk of malignant potential and its carcinogenesis rate was 0.40% to 6.25%. Oral squamous cell carcinoma (OSCC) was the most common malignant tumor in the oral cavity, accounting for more than 80%. We could see a few of OLP turned into OSCC clinically. The former researches have showed that the occurrence and progression of OLP and OSCC were connected with a lot of factors, especially connected with the abnormal expression of certain oncogene and anti-oncogene.A recently discovered gene, p63, was a member of the p53 gene family and harboring different isoforms by alternate splicing. The two main isoforms, TAp63 andΔNp63, have opposite functions, being responsible for cell-cycle arrest and cell proliferation respectively. P15, as an anti-apoptotic gene, arrest cell cycle progression mainly by inhibition of CDK4/6, further preventing the occurrence of tumor. Mdm2 was an oncogene, overexpression of mdm2 was found in a wide variety of human tumors, such as lung cancer, esophageal squamous cell carcinoma, laryngeal squamous cell carcinoma et al. At present, the study on the expression of p63, p15 and mdm2 in OLP and OSCC was still rare.ObjectiveTo detect the expression of proteins of p63, p15 and mdm2 in human normal oral mucous, oral lichen planus and oral squamous carcinom by immunohistochemistry, and investigate their role in occurrence and progression of oral lichen planus and oral squamous carcinom, then offer theoretical basis for canceration of oral lichen planus and early diagnosis and treatment of oral squamous carcinom.Materials and methods1. SpecimensAll the specimens were obtained form the pathology archive files of the department of pathology of Zhengzhou University and the biopsy and operation in the department of Stomatology. These specimens include 46 case of OLP(26 case of OLPⅠ,20case of OLPⅡ),42 case of OSCC(14 case of OSCCⅠ,13 case of OSCCⅡand 15 case of OSCCⅢ) and 15 case of normal oral mucous were taken as normal control. There were 15 cases with lymph node metastasis of all OSCC.2. Immunohistochemistry (s-p)(1) Key step:For all cases, cut paraffin blocks by serial section at 3μm, put these sections in calorstat of 60℃about 3 hours, then make a series of operation according to the specification.(2) Standard of determination:to take nucleus/cytoplasm of apparent brown/ brown particles with clear background as positive staining. Both p63and mdm2 were expressed in the nucleus. P15 was mainly expressed in the nucleus, so were a small number of cytoplasm specimens. Observe 5 Kens randomly under the high power lens, then classifies the dyeing result according to the proportion of the positive cell: no dyeing or positive rate≤5% is (-),6%～30% is (+) ,31%～50% is (++) >50% is (+++)(3) Statistics:statistical analysis all date was dealt statistically with SPSS10.0.Result1. P63 Protein has a significant expression in normal tissue, but a lower expression in the OLP and OSCC than normal tissue. And there are a significant differences among the three groups(P<0.05); OLPⅠshowed significantly higher expression than OLPⅡ(P<0.05), But there are no statistical significances among different pathological classification of OSCC (P>0.05)2. P15 Protein presented a significantly higher expression in normal oral mucosa than OLP and OSCC, From oral normal mucosa, OLP to OSCC, its expression tapers off. The difference between the two types of OLP has no statistical significance (P> 0.05). But there is statistical significance in different pathological classifications of OSCC(P<0.05)3. Mdm2 protein is negatively expressed in group of normal oral mucosa, while it is positively expressed in group of OLP and OSCC, the positive rate of mdm2 protein in OLP and OSCC are 7%(3/46) and 71.4%(30/42) respectively, and there are statistical significant between the there groups (P<0.05). The difference in different type of OSCC and OLP all have no statistically significance (P>0.05)4. There are significantly positive correlation between mdm2 protein expression and p63 protein expression in OSCC (r=1.00, P=0.000<0.05).5. There are significantly negative correlation between mdm2 protein expression and p15 protein expression in OLP(r=1.00,P=0.000<0.05).6. The positive rate of p63 and mdm2 protein in groups of OSCC with lymph node metastasis was significantly higher than groups of devoid of lymph node metastasis(P <0.05), but the positive rate of p15 protein in groups of OSCC with lymph node metastasis was significantly lower than groups of devoid of lymph node metastasis(P <0.05).Conclusion1. P63 ptotein might be associated with the lymph node metastasis of OSCC, but it still need further study.2. The law expression of p15 protein is associated with pathological classification and lymph node metastasis, which suggests that its law expression might be play an important role in the occurrence and progression of OSCC. 3. Mdm2 protien presents a high expression in OSCC, it suggests that mdm2 might be associated with the occurrence of OSCC, and its overexpression might be regarded as an early molecular event of OSCC.4. P15 and mdm2 might have interactions in the progression of OLP, and might be early markers to predict whether OLP has a risk of the cancerization.5. The joint detection of the protein expression of p15 and mdm2 might offer theoratical foundations for the early diagnose and formulating an effective treatment plan of OSCC.6. In the processes of OSCC, p63 might correlate with mdm2.