Expression Of Stem Cell Markers Cd133,nestin And Cd44 In Malignant Melanoma And Its Significance

Stem cells are initial cells which have the ability of self-renewal,infinite multiplication as well as multi-directional differentiation potential.Many research indicated that marrow,nervous system and prostate gland have stem cells.Cancer stem cells are a small portion which have the nature of stem cells in the cancer cells, with the ability of infinite self-renewal,high multiplication as well as multi-directional differentiation potential.It can produce different phenotype cancer cell,forms the new tumor.It has been confirmed that cancer stem cell exist in leukemia and solid tumors such as breast cancer,brain tumor,prostatic carcinoma, ovarian cancer.Malignant melanoma(MM) is a highly malignant tumor which often occurred in the skin.The incidence rate of MM is the third one in the cutaneous malignant tumors(6.8%～20%),while the mortality rate accounted for 80%of the number of the cutaneous malignant tumors.Over the past 10 years,both of the incidence and mortality rate of MM were significantly increased in the worldwide scale.The main goal of the traditional treatment such as radiotherapy,chemotherapy and surgical resection is to remove or kill the tumor tissue and tumor cells,reduce tumor size and number,but the problem of tumor recurrence,metastasis,chemical resistance and various treatment toxicity and so on can not be resolved.To cure MM,we must find out the source of the tumor and eradicate it.The theory of cancer stem cells make the targeting of anti-cancer stem cells and eradicating the tumor is possible.So far, domestic reports about MM stem cells have not been reported,a few literatures has been reported abroad.CD133 is a five transmembrane glycoprotein on the surface of cell which is 120KD.The prominent feature of its expression is reduced rapidly with the cell differentiation,which makes it a unique molecular markers for separating and identificating stem cells or progenitor cells,it expresses in the bone marrow and peripheral blood stem cells and endothelial progenitor cells,while the mature endothelial cells do not express.CD133 can promote angiogenesis,involved in signal transduction.The study found that CD133 is also expressed in the stem cells or progenitor cells of the other systems,such as neural stem cells,embryonic stem cells, prostate stem cells and so on,recently,it has been proved to be one of the marks of brain tumors and prostate tumor stem cells.Nestin is a intermediate filament present in neuroepithelial stem cells,which express in undifferentiated neural stem cells and thought to be a marker of neural stem cells.The study found that Nestin is also expressed in the central nervous system stem cells,pancreatic stem cells and gastrointestinal stem cells.It is confirmed that Nestin is one of the cell marks of the brain tumor stem cells.CD44 is a glycoprotein and a member of cell adhesion molecules,which mainly expresses in the surface of some normal epithelial cells,mesenchymal cells or some specific tumor cells.It plays a catalytic role in the immune recognition,lymphocyte homing and intercellular adhesion,cell-matrix interactions,as well as the movement of cells.Research has shown that the occurrence,development,recurrence and metastasis of the tumor are closely related,It has been confirmed CD44 is one of the surface markers for prostate stem cells,ovarian cancer stem cells,breast cancer stem cells,prostate cancer and lung cancer stem cell.In order to discuss the expression and significance of stem cell markers in the MM and intradermal nevus tissues.We use immunohistochemistry to study the expression of CD133,Nestin and CD44 to further confirm the existence of cancer stem cells in MM and provide clues to sorting and identification malignant melanoma stem cells. Material and Methods1.The expression of three markers in MM and intradermal nevus tissues were detected by immunohistochemistry.2.Statistics processing:All the statistical analyses were performed by the SPSS10.0 software package and expressed with(?)±S.The comparisons of the positive expression rate of CD133,Nestin and CD44 between MM and intradermal nevus were carried by Chi-square with the counting material.The comparison of each marker between MM and intradermal nevus was carried by the t-test.Correlation coefficient calculated by Pearson.α=0.05 was considered to be of statistical significance.Results1.Expression of CD133The positive expression rate of CD133 in MM and intradermal nevus were 53.33%(16/30)and 23.33%(7/30)respectively,the difference of CD133 between MM and intradermal nevus was of statistically significant(χ~2=5.711,P=0.017).The percentage of positive cells of CD133 in MM and intradermal nevus were 2.98%±5.62%and 0.10%±0.21%respectively,the difference of CD133 between MM and intradermal nevus was of statistically significant(t=2.801,P=0.007).The positive cells of CD133 in MM are different in size,with round,oval, spindle,polygonal shapes and scattered,cord-like or nest-shaped distributions. However,The CD133-positive cells in intradermal nevus are more similar in size and with round,oval shapes and scattered distributions.2.Expression of NestinThe positive expression rate of Nestin in MM and intradermal nevus were 80.00%(24/30)and 53.33%(16/30)respectively,the difference of Nestin between MM and intradermal nevus was of statistically significant(χ~2=4.800,P=0.028).The percentage of positive cells of Nestin in MM and intradermal nevus were 34.92%±34.89%and 7.26%±13.13%respectively,the difference of Nestin between MM and intradermal nevus was of statistically significant(t=4.065,P=0.000). The positive cells of Nestin in MM are different in size,with round,oval,spindle., polygonal shapes and scattered,block-shaped or nest-shaped distributions.However, The Nestin-positive cells in intradermal nevus are more similar in size and with round. oval shapes and scattered,small nest-shaped distributions.3.Expression of CD44The positive expression rate of CD44 in MM and intradermal nevus were 20.00%(6/30)and 0(0/30)respectively,the difference of CD44 between MM and intradermal nevus was of statistically sigrfificant(χ~2=6.667,P=0.010).The percentage of positive cells of CD44 in MM and intradermal nevus were 1.28%±3.26%and 0 respectively,the difference of CD44 between MM and intradermal nevus was of statistically significant(t=2.153,P=0.037).The positive cells of CD44 in MM are different in size,with round,oval,spindle, polygonal shapes and scattered,small nest-shaped distributions.However,the expression of CD44 in intradermal nevus is negative.4.No correlation was found in each group between the percentage of positive cells and sex,age and the course of disease(P＞0.05).Conclusions1.The expression of stem cell markers CD133,Nestin and CD44 is different in MM cancer cells,suggesting the existence of cancer stem cells in MM.2.The expression of stem cell markers CD133 and Nestin is low in intradermal nevus,suggesting the existence of melanocyte stem cells in intradermal nevus.