The Expression And Correlation Analysis Of PTEN, PIP3/MAPK, Cyclin D1/CDK4 In Oral Squamous Cell Carcinoma

Objective: The objective of this study was to detect the expression of PTEN, PIP3, MAPK, Cyclin D1 and CDK4 in the oral squamous cell carcinoma (OSCC) and precancerous lesions, and analyze the role of PTEN in OSCC pathogenesis. The relationship of PTEN with PIP3, MAPK, Cyclin Dl and CDK4 was evaluated to testify whether PTEN can affect the signaling pathways, and then regulate the cell cycle so that PTEN can suppress the cell growth.Methods: Immunohistochemical staining with SP methods was used to detect theexpression of PTEN, PIP3, MAPK, Cyclin Dl and CDK4 in 63 OSCC cases, 11 oral dysplasia cases, 11 oral simple hyperplasia cases and 12 normal oral mucosa cases. Statistic and correlation analyses were applied to analyze the results.Results: The negative or low expression rate of PTEN in OSCC was 25%(16/63), which was remarkably lower than the normal, simple hyperplasia and dysplasia groups. The positive rate of PIP3 in simple hyperplasia, dysplasia and OSCC were 66 % (19/29) ,82% (9/11) and 68% (43/63) respectively, which was much higher than the normal groups. The positive rate of MAPK in dysplasia and OSCC were 82% (9/11) and 84% (53/63) respectively, which was much higher than the normal and simple hyperplasia. The positive rate of Cyclin D1 in OSCC was 49% (31/63) , which was significantly higherthan normal, simple hyperplasia and dysplasia groups. The positive rate of CDK4 in dysplasia and OSCC were 91%(10/ll) and 97%(61/63), significantly higher than normal and simple hyperplasia(P<0. 01) .The correlation analyses revealed that a significantly negative relationship of PTEN with PIP3, Cyclin Dl and CDK4. There was no correlation between PTEN and MAPK. A positive relationship of PIP3, MAPK with Cyclin Dl and CDK4 were observed. The correlation between Cyclin Dl and CDK4 was positive.Conclusion: (1) The results suggest that PTEN, PIP3, MAPK, CyclinDl and CDK4 may play a role in the pathogenesis of OSCC. (2) In OSCC and precancerous lesions, PTEN may down-regulate the expression of PIP3, and then down-regulate the expression of Cyclin Dl and CDK4 through PIP3 signaling pathways, which leads to the cell death. (3) These data also suggest that in OSCC and precancerous lesions, some factor other than PTEN may affect the expression of Cyclin Dl and CDK4 through MAPK signal transduction pathways, and finally the cell growth is suppressed.