Expression Of Mcm5 And Its Significance In Cervical Pathological Changes

Background: Minichromosome maintenance proteins(MCMs)are a group of proteins closely related with the DNA replication,consisting of MCM2,MCM3,MCM4(Cdc21),MCM5(Cdc46),MCM6(Mis5) and MCM7(Cdc47).MCM proteins are important member of replication licensing factor(RLF),which indicate the start of the initiation of DNA replication bonding with the chromatin before the initiation of DNA replication.MCM Proteins are only present with in the nucleus throughout the cell cycle,the mRNA levels of MCM proteins in the normal cells changes with the cell cycle. Its expression reach to peak in G1/S conversion,and in Go phase,differentiation or apoplexies,the mNRA levels of MCM proteins declined to so little that can not be detected.MCM proteins express in high level in proliferating cells,and in low level or never in GO phase cells or differentiated cells,so MCM Proteins may be a special marker of Proliferating cells. Tumour cells compared with normal cells display a quick proliferation capacity on the functional status besides the characteristics of morphology. Therefore,MCM proteins can be used in tumour research.MCM5,as a member of the MCM Proteins,can response MCM Proteins level. A series of studies of MCM5 expression including esophagus,cervix and bladder show that MCM5 is a good markers and Diagnosis Tool for cell proliferation. But it has not reported systematically to the study about MCM5 expression and clinical significance in chronic cervicitis, cervical intraepithelial neoplasia(CIN)and Cervical Squamous Cell Caricinoma.Objective: To investigate the relationship between MCM5 expression and clinical pathology parameters in chronic cervicitis, cervical intraepithelial neoplasia and cervical carcinoma..Methods: We examined the expression of MCM5 with immunohistochemical stain in chronic cervicitis (n=30), CIN I (n=30), CIN II (n=30),CINIII (n=30),and Cervical Squamous Cell Caricinoma (n=66).By calculating a labeling index (LI), we compared the pattern and LI of MCM5 expression in chronic cervicitis and CIN and Cervical Squamous Cell Caricinoma, and an analysis of theassociation between MCM5 expression and clinicopathological characteristics of Cervical Squamous Cell Caricinoma was also carried out. The statistical software SPSS13.0 was used to analyzed the data. Comparison among multiple groups using Kruskal-Wallis test and Comparison between two independent samples of group using Wilcoxon test, p<0.05 was considered the level of significance.Results: MCM5 positive staining was located in nucleus. Stain was restricted to the nuclei of basal epithelial cells with some cells in 1～2 suprabasal layers in the tissue of chronic cervicitis.The postive cells ascended with the progress of CIN.The postive cells obviously increased in squamous cancer and lost the regular distribution with mostdispersion in the complete layers of epithelial and invasion the subjacent cervical stroma. The expression of MCM5 protein in different cervical tissue:The expression of MCM5 protein gradually increased from chronic cervicitis to invasive cancer.Among the group of chronic cervicitis,the group of CINⅠ,the group of CINⅡ,the group of CINⅢand the group of Cervical Squamous Cell Caricinoma,there was significant difference with each other(P<0.05).The median of MCM5 LI in normal gastric mucosa was 5.05%(0～10.12%). The median of MCM5 LI in CINⅠwas 36.45%(20.14%～50.55%)., The median of MCM5 LI in CINⅡwas 60.43%(41.11%～74.56%), The median of MCM5 LI in CINⅢwas 79.52%(64.78%～85.21%),In cervical squamous cell caricinoma,MCM5 expression was seen throughout epithelium,The median of MCM5 LI in cervical squamous cell caricinoma was 90.34%(76.11%～94.89%), including in surface cervicalcytes. The differences between chronic cervicitis and cervical squamous cell caricinoma were of statistical significance (P<0.01). The expression of MCM5 protein gradually increased from chronic cervicitis to invasive cancer.Among the group of chronic cervicitis,the group of CINⅠ,the group of CINⅡ,the group of CINⅢand the group of cervical squamous cell caricinoma,there was significant difference with each other(P<0.05).The expression of MCM5 tended to decrease with the increasing differentiation degree of cervical squamous cell caricinoma. There was no statistical significance between MCM5 expression and some clinico-pathological characteristics such as age,FIGO clinical stages and lymph node metastases (P>0.05).Conclusion: 1.The experiment shows that MCM5 may serve as a reliable proliferation marker in cervical squamous cell caricinoma. and CIN, MCM5 expression is a marker of cervical tissue;2.According to the distribution range and LI of MCM5 expression,it is feasible to discriminate between chronic cervicitis and CIN and cervical squamous cell caricinoma.As MCM5 expression is related to the grade of cervical squamous cell caricinoma,it can predict the degree of differentiation in cervical squamous cell caricinoma. As MCM5 expression is related to the grade of cervical squamous cell caricinoma It implies that MCM5 is a novel marker for cell proliferation and has potential to be a better marker for cervical squamous cell caricinoma.3. MCM5 expression is related to the differentiation of cervical squamous cell caricinoma, can indirectly reflect the vicious degree of cervical squamous cell caricinoma.