| Background:Accumulating evidences confirm the relationship between disproportional cell cycle modulation and the tumorigenesis. cyclin Dl and p27 mainly participate in the modulation of the control of G1-S period transition, a key check-point in the cell cycle, cyclin Dl serves as a positive controlling factor mainly through pRB pathway, while p27 serves as a negative factor by restraining cyclin-CDK complex. Salivary adenoid cystic carcinoma (SACC) is one of the most common malignancies of the salivary glands, but the expression of cyclin Dl and p27 in ACC is not well defined yet.Objective:The aim of this present study is to investigate the expression of cyclin Dl, p27 and Ki-67 in SACC, to assess the significance of them in the carcinogenesis and development of SACC, and to evaluate the possibility of using them as the biological markers of SACC based on the analysis of clinicopathologic parameters.Methods:Formalin-fixed and paraffin-embedded tissue specimens from 41 cases of SACC, 15cases of pleomorphic adenoma(PA) and 12 cases of normal salivary gland (NSG) were re-examined histopathologically, and the expression ratio and labeling indexes (LI) determined for cyclin D1, p27, Ki-67 with immunohistochemical staining method. Statistical analysis was performed with SPSS 10.0 software, using Chi-square, Fisher's exact test, Wilcoxon test, K-W test and Spearman test. Statistically significant level wasconsidered as "alpha equals 0.05". Results:1. The positive immunostaining of cyclin Dl, p27 and Ki-67 was mainly observed in the nucleus with only few cytoplasraic staining of cyclin Dl and p27.2. The cyclin Dl positive immunostaining ratio and cyclin Dl LI were significantly higher in SACC (68.3%,44.63)than those in NSG(0%,2.35) (P<0.05),and the cyclin Dl LI in SACC (44.63) was significantly higherthan that in PA(16.57) (P<0.05). There was a correlation between the cyclin Dl LI and TNM stage of SACC (P<0.05).3. The p27 high positive ratio and p27 LI in PA(86.7%, 57.10) and those in NSG(100%, 51.35) had no significant difference(P>0.05). Reduced expression of p27 was found in SACC(31.7%, 23.17 ), significantly differed from PA and NSG (P<0.05). p27 LI was correlated with metastasis of SACC (P<0.05).4. The Ki-67 positive ratio and Ki-67 LI were significantly higher in SACC (58.5%, 20.22) than those in PA(0%, 3.44) and NSG(0.0%, 0.00) (P<0.05). Differences in both the Ki-67 positive ratio and Ki-67 LI were found between the two pathological subtypes of SACC (P<0.05).5. The expression of cyclin Dl had a positive correlation with that of Ki-67(P<0.05), while there was a negative one between the expression of p27 and Ki-67. No significant correlation was found between the expression of p27 and cyclin D1(P>0.05).Conclusion:l.Dysregulation of the Gl-S transition of the cell cycle is a frequent event in the initiation and development of SACC.2.The overexpression of cyclin DI and reduced expression of p27 might accelerate the progress of the cell cycle and promote the carcinogenesis and proliferation of SACC.3.The overexpression of cyclin Dl might be a relatively early event in the initiation of SACC.4.Ki-67 might be helpful to differentiate SACC from benign salivary tumors.5.Multiple analysis of the expression of cyclin Dl , p27 and Ki-67 might be useful for us to make the diagnosis and to assess the biological behavior of SACC.
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