Expression Of Mcm2 And Its Significance In Colorectal Neoplasm

PURPOSE Minichromosome maintenance proteins(MCMs) are members of the prereplicative complex that is essential for eukaryotic DNA replication. They are only present within the nucleus throughout the cell cycle, but rapidly downregulated in differentiated cells. Recent studies have demonstrated MCMs are novel proliferation markers for dysplasia and tumor. The aim of this study is to determine the pattern and frequency of Mcm2 (a member of the family of MCMs) expression in colorectal normal mucosa, adenoma and cancer, and to assess the relationship between Mcm2 expression and clinicopathological characteristics of colorectal cancer. In this study, the expression of Mcm2 is also compared with the expression of Ki-67 and PCNA, another two kinds of markers for cell proliferation, to determine which is a better marker for colorectal neoplasms.METHODS We examined the immunohistochemical staining of Mcm2 in colorectal normal mucosa(n=23), adenoma(n=33), and cancer(n=69), and quantified Mcm2 expression by calculating a labeling index(LI). And then, the pattern and LI of Mcm2 expression in normal mucosa, adenoma and cancer were compared, and an analysis of the association between Mcm2 expression and traditional clinicopathological characteristics of colorectal cancer was also carried out. The expression of Mcm2 was also compared with Ki-67 and PCNA. RESULTS Mcm2 expression in normal colorec tal mucosa is confined to thebasal third to half of colonic crypts but no expression in surface coloncytes. The median of Mcm2 LI is 18%(5%~37%)in normal colorectal mucosa. In colorectal adeoma and cancer, Mcm2 expression is seen throughout epithelium, including in surface coloncytes. The median of Mcm2 LI in adenoma and cancer are 35%(15%-75%) , 66% (41%-90%) respectively. The differences between normal mucosa, adenoma and cancer are of statistical significance (P< 0.001). There is no statistical significance between the LI of Mcm2 and some clinicopathological characteristics such as age, sex, dimension, histopathology, Dukes stage, lymph node metastases and distant metastases. A significant association is also demonstrated between Mcm2 LI and the grade of colorectal caner and adenoma. Compared with the staining of Ki-67 and PCNA, Mcm2 stained a percentage of nuclei intermediate between Ki-67 (lowest) and PCNA(higest) in same tissues, and it is a better marker related to the grade of colorectal neoplasms. CONCLUSION These data support the evidence that Mcm2 may serve as a reliable proliferation marker in colorectal tissue and according to the pattern and LI of Mcm2 expression, it is feasible to discriminate between normal tissue, adenoma and cancer. It also implys that Mcm2 maybe a better diagonostic marker for colorectal neoplasms than other markers such as Ki-67 and PCNA. In addition, as Mcm2 LI is related to the grade of colorectal neoplasms, it can predict the degree of differentiation in colorectal neoplasms, which can help to predict the clinical prognosis.