The Expression And Significance Of PTEN, MMP-9, And CD4/CD8 In Status Lymph Node Metastasis, Micrometastasis And Isolated Tumor Cells Of Breast Cancer

The status of regional lymph node metastasis acting as an important role on the diagnosis and treatment of the breast cancer,at the same time,it is the key independent prognosis factor.The micrometastasis and isolated tumor cells were defined by AJCC Cancer Staging Manual 6th ed.that diameter of tumor micrometastasis ranged from 0.2mm to 2mm,with malignancy cell activity,the isolated tumor cells(ITCs) was less than 0.2mm in diameter and without malignancy cell activity.The developing course of regional lymph node metastasis is from the isolated tumor cells to micrometastasis and to result in extensive metastasis in lymph node.It is not clear the mechanism of the isolated tumor cells or the cluster of tumor cells how to surmount the leukomonocyte around it and growth and development.In clinic,it also have dispute。Some researchers had reported that 15%～90%of the breast cancer patients without metastasis were positive in the isolated tumor cells among the axillary lymph nodes.So the isolated tumor cells were regareded as a index of the evaluation of prognosis and adjunctive treatments,can help doctors to decide whether to choose the adjunctive therapy or not..PTEN gene,the anti-oncogene like the p53,has a close relationship with tumorigenesis.The function of the antitumorigenesis chiefly depend on the activity of lipid phosphatase,which interfere the signal transduction of t PKB/Akt.Matrix metalloproteinascs(MMPs) are a kind of endocrine protease depended on the ion of zinc.The MMP-9 is one of the MMPs' family,that hydrolyze the collagens and galantine of external matrix,promote the tumor cell invade into the other tissue around the cancer through the absent basement membrane.CD4~+ lymphocyte plays a key role on the immunological priming and intensity by regulation the activity of other cells through secretion of the cytokines.The cells can activate the B lymphocyte,inducing the humoral immunity.CD8~+ lymphocyte,The CD8~+ T lymphocyte can kill the target cells specificly.The ratio of CD4~+ T/CD8~+ can directly reflect the status of the cellular immunity function,which is important for the judgement of the level of body immunologe function. The aim of this study detected the expression of PTEN,MMP-9,and CD4/CD8 in lymph node metastasis,micrometastasis and isolated tumor cells in breast cancer,inorder to investgate their significances in the developing course of metastasis.Materials and Methods:Between June 2005 and Mar 2006,92 female breast cancer operating patients underwent the axillary lymph node dissection at The Center of Breast Disease of the Southwest Hospital.293 lymph nodes were collected for the study.The expression of CK19 and SMA in the lymph nodes were detected by immuohistochemical method to check out the lymph nodes which contain metastasis,micrometastases,or ITCS.The expression of PTEN,MMP-9 and CD4/CD8 were then detected by immuohistochemical method.All the results were statistically analyzedResults:1.In all the 293 lymph nodes,145 nodes(49.49%)were no metastasis,84 nodes(28.67 %)had metastases,42 nodes(14.33%) had micrometastases,and 22 nodes(7.51%)had ITCs.The environment of All around tissue of metastases and 80.95%of micrometastases expressed SMA.2.All metastastic nodes had low expression of PTEN.Among 42 micrometastasis nodes,38 nodes had low expression of PTEN,and the rest had no expression.All metastasis nodes had expression of MMP-9,and 66 nodes(78.57%)had high MMP-9 protein level. Among 42 micrometastastic nodes,1 node(2.38%)had high expression of MMP-9,18 nodes(21.43%)had middle expression,15 nodes(35.72%)had low expression of,and 2 nodes(4.76%)had no expression.Among 22 nodes which had ITCs,3 nodes expressed MMP-9 in low level,and th rest had no expression.3.The rate of CD4~+ lymphocyte had signifcant difference between metastastic and non metastastic groups(P＜0.05),and also had significant difference between metastasis and micrometasatis groups(P＜0.05).The rate of CD8~+ lymphocyte did not have significant difference among metastastic,micrometasatic and non metastastic groups(P＞0.05).There were significant difference of rate of CD4~+ T/ CD8~+ T between metastastic and no metastastic groups(P＜0.05),whereas were no significant difference of that between no metastastic and micrometastastic groups(P＞0.05).Conclusions:1.The variation of actin in stromal reaction of axillary lymph nodes may play the key role in the mechanism from the isolated tumor cells in lymph node developing to micrometastastic or metastastic course.2.The high expression of MMP-9 and the low expression of PTEN may enhance the capability of invasion and metastasis of tumor cells.3.CD4~+ lymphocytes incresed on site of tumor cells in the region of lymph nodes, which raised the ratio of CD4~+ T/ CD8~+ T.It indicates that the development of tumor cells is the variation of immune response to tumor cells and may be one cause of the tumor cell developing.