The Expression And Correlation Of CyclinD1, P27 And PTEN Protein In Human Oral Lichen Planus And Human Squamous Cell Carcinoma

BackgroudAs a common oral mucosal diseases associated with abnormal keratinized mucosa, Oral Lichen Planus (OLP), which is second only to the incidence of recurrent aphthous ulcers, is a chronic superficial noninfectious inflammatory disease. The attack rate of OLP is about 0.22%～1% in our population, WHO had regarded OLP as a precancerous conditions in 1972 because of its potential with cancer. Oral Squamous Cell Carcinoma (OSCC) is the most commentest malignant tumor in the oral and maxillofacial, accounting for more than 80%, and accounts for 3%～5% in the whole body tumor. We could see a part of OLP may transformed into OSCC clinically, particularly the risk of malignant can be increased in erosive OLP. The former results show that multi-stage, multi-gene, many factors result in the occurrence and progression of OLP and OSCC. One of the main features of tumor is the regulation of cell proliferation disorders in the process of cell cycle.Most of the studies suggest that CyclinDl protein which is closely related to the cell cycle is a proto-oncogene, as the key protein in the regulation of cell proliferation, it can prompt cells from G1 to S phase, and its overpression led to the occurrence and progression of malignant tumor. P27 protein is a cyclin-depender kinase inhibitor which plays an important negative regulation role in the progression of cell cycle and is considered a tumor suppressor gene in its function of involving the cell proliferation, differentiation and apoptosis, as the rate-limiting factor in G1 phase of cell cyclin, it can prevent cells from G1 to S phase. PTEN is the first gene we ever found which has dual-specificity phospatase activity with the tumor suppressor gene, PTEN can lead to arrest and apoptosis in cell cycle through regulating the signal molecules in cell signaling pathway, thereby inhibiting the development, invasion and metastasis in tumor. Currently, the study on the expression and relationship of CyclinD1, P27 and PTEN is rarely reported. ObejectivesTo detect the expression of CyclinDl, P27 and PTEN protein in normal oral mucous, different type of oral lichen planus and oral squamous cell carcinoma of different histological grade by immunohistochemistry, to investigate the possible roles in the carcinogenesis process of oral lichen planus and the possible clinical significances, then provide clinical detection in malignant potential of oral lichen planus and early clear diagnosis and treatment in oral squamous cell carcinoma with a theoretical basis.Materials and methods1. Materials All specimens of formalin fixed, paraffin-embedded which have a complete clinical and pathological data are selected from the archive files in the Department of Pathology of the First Affiliated Hospital of Zhengzhou University and the biopsy and operation in the department of Stomatology. These specimens include 46 cases of oral lichen planus(26 cases of non-erosive type,20 cases of erosive), 42cases of oral squamous cell carcinoma(14 cases of OSCC I,15cases of OSCCⅡ, 13 cases of OSCCⅢ) and 14 cases of normal oral mucosa were taken as a control group.2. Methods The expression of CyclinDl, P27 and PTEN were detected in normal oral mucosa, different type of oral lichen planus and oral squamous cell carcinoma through immunohistochemical S-P, and the results were compared with histological type, histological grade,biological behavior.3. Statistics All states were statistically analysed with SPSS17.0.Statistical analysis of qualitative data applied x 2 test,of quantitative data applied Kruskal-Wallis test.Possible correlations between variables of the analyzed samples were examined by Spearman test.Statistically significant level was considered as "alpha equals 0.05",Results1. The positive cells localized in the nucleus.There were 2cases(15.4%) were positive for expression in 14cases of normal oral mucosa; 7 cases(26.9%) were positive for in 26 cases of non-erosive OLP,9 cases(45.0%) were expression in 20 cases of erosive OLP; 9cases(64.3%) showed positive expression in OSCC I,llcases(73.3%) showed positive expression in OSCC II,7cases(84.6%) were positive in OSCCⅢ, showing that the intensity of CyclinDl was enhanced with increasing grade malignancy, there was significant difference in pathological classifications (P<0.05).We could see that the positive expression rate in oral mucosa, oral lichen planus and oral squamous cell carcinoma was increasing trend, the expression of each group was significant difference(P<0.05).2. The overexpression of P27 protein was localized in the nucleus.There was only 1 cases(7.1%) normal oral mucosa in 14 P27 protein display negative expression, and the positive rate was 92.9%; the positive rate of P27 protein in non-erosive OLP,erosive OLP and OSCCⅠ, OSCCⅡ, OSCCⅢwere 88.5%,75.0%,71.4%,46.7%, 23.1%, we could see the positive rate reduced in turn. The enpression of each group was significant differential (P<0.05),and the higher the degree of maglignancy, the lower its expression, there was significant difference in pathological classifications (P<0.05)3. The positive expression of PTEN protein was mainly localized in the cytoplasm, but there was few specimens were positive for nuclear expression simultaneously. All of cases in normal oral mucosa displayed positive expression and the positive rate was 100%. the positive rate of P27 protein in non-erosive OLP, erosive OLP and OSCCⅠ, OSCCⅡ, OSCCⅢwere 92.3%,85.0%,71.4%,53.3%, 30.1%, we could see the positive rate reduced in turn. The enpression of each group was significant differential (P< 0.05), there was significant difference in pathological classifications (P<0.05).4. In oral squamous cell carcinoma, there was significant negative correlation between P27 protein expression and CycliDl protein expression (r=-0.408, P=0.008 <0.05), significant negative correlation between CycliD1 protein expression and PTEN protein expression (r=-0.351,P=0.023<0.05), significant positive correlation between PTEN protein expression and P27 protein expression (r=0.623,P=0.000< 0.05)Conclution 1. The abnormal expression of CyclinDl might be involved in the carcinogenic process of OLP, and its expression might be an early event and associated with poor prognosis in OSCC.2. P27 protein might be involved in the occurrence of OLP and OSCC, and to some extent might reflect the prognosis of OSCC.3. The mutation or loss expression of PTEN gene played an important role in the occurring of OLP and OSCC.4. CyclinD1, P27 and PTEN protein may play a synergetic role in the occurring and developing of oral squamous carcinoma.