The Expression And Significance Of C-kit In Ectopic Endometrium

Endometriosis(EMs) is the ordinary disease happen in gynecologic area. The disease incidence rate may reach from 3% to10% in the child-bearing age women. Although it is benign pathological changes,it has aggressive and evaluative behavior of malignant tumor. At present,it still isn't clear about the endometriosis pathogenesis. There are lots of theories, theory of 'retrograde menstruation' has been accepted by the most people. While 90% woman might have the 'retrograde menstruation'. but only little had the endometriosis. This means 'retrograde menstruation' was only a cause of endometriosis. Endometriosis interna is defined that endometrial gland and mesenchyma invade tunica muscuaris uteris. EMs and endometriosis interna both belong to ectopic endometrium disease. There are various kinds of theories about etiopathogenisis and pathogenesis of endometriosis interna. Recently, the multi-factors theory has been considered as the pathogenesis, anti-apoptosis is one of causes of endometriosis. The endometrium in abdominal cavity or peritoneum which outside of uterus grows abnormally. First of all, Ectopic endometrial tissue must have to resist apoptosis and activeness. Secondly, blood vessel supports the nutrition of endometrium. Currently, many research have proved that the formation of Endometriosis is effected by anormal-apoptosis。It is the fact that Gene mutation cause c-kit acceptor (CD117) activate, further cause cell proliferation and inhibited apoptosis。C-kit is expressed at normal endometria ,but the over expression of C-kit may suppressed the perish of cell in endometrium. And then, the activeness of endometrium is improved. Meanwhile, C-kit participates to shape the blood vessel of endometriosis. This article discuss the relationship between C-kit protein expression and accretion of ectopic endometrium. Through experiment to observe and detect the expression of C-kit from eutopic endometrium ,ectopic endometrium and normal endometrium. Those eutopic and ectopic endometrium were obtained from endometriosis of ovary and peritoneal, adenomyosis.There are 94 tissue simples were obtained from ChangChun Gynecological and Obstetrical Hospital and SiPing Women and Chidren Hospital. Experimental group: ectopic endometrium and entopic endometrium from endometriosis and endometriosis interna. Samples come from those two hospital. In face, there are 48 women with endometriosis and endometriosis interna have surgery from Jan. 2005 to Nov. 2006. (22 women with endometriosis interna, 18 women with ovarian endometriosis, 8 women with peritoneal endometriosis). Endometrial samples were obtained in the proliferative stage of the menstrual cycle in 38 cases and in the secretory phase in 10 cases. The mean age is 35.8±6.5years. No difference in age was found in all ectopic endometrium groups(P>0.05) .16 eutopic endometrial samples were obtained from women who have hysterectomia with above-mentioned endometriosis and endometriosis interna. 12 cases in the proliferative phase and 4 cases in the secretory phase. Control group:30 endometrial specimens were obtained from women with emmenia disorder or hysterectomia. 19 cases in the proliferative phase and 11 cases in the secretory phase, the average age is 35.5±6.0 years. The result was approved by pathological confirmation. Menstrucal cycle was defined by the last period and the pathological result of endometrial tissue. No difference in age was found in research group and compare group(P>0.05). Hormone wasn't used in first three months before patients have operation.After numbering, the tissues were fixed in neutral-buffered 10% formalin solution. Then 4-5 um thickness paraffin-embedded sections were cut. All of sections were confirmed by pathological confirmation again. The sections were immunostained using the SP immunohistochemically,DAB coloration, cell nucleus were counterstained with haematoxylin. And then determine C-kit expression through comparing the section of ovarian cancer with strong C-kit. In order to evaluate the C-kit expression of normal endometrium, ectopic endometrium and eutopic endometrium of endometriois and endometriosis interna. There are 10 regions which are not overlap were chosen in 400 times of vision for each tissue. According to the percentage of masculine cell and intensity of colouring, each tissue was divided into four ranks in terms of (-),(+),(++),(+++).The result was made by using statistical processing analysis.The results of the study :①Positive expression of C-kit is shown as brown and yellow granule in cytoplasm and cytolemma of glandular epithelia, mainly in cytoplasm. The expression of C-kit in all endometria ,which includes normal endometria, eutopic endometria and ectopic endometria.②The expression of C-kit mainly is weakly positive in normal endometria group,the expression rate is 90%. The expression of C-kit is not diversity during menstrual cycle.③C-kit was excessively expressed in ectopic endometrium of endometriosis interna, ovarian and peritoneal endometriosis.④The eutopic endometrium(++～+++)positive expression of C-kit were higher than normal endometrium (++～+++). But there is not too much differnce between them (P>0.05). The (++～+++)positive expression of C-kit rate in eutopic endometrium group was 31.2% and in normal endometrium group was 10%.⑤The C-kit expression in ectopic endometrium group is highest than eutopic endometrium group and normal endometrium group. And there was obvious difference between them(P<0.05). The(++～+++)positive expression rate of C-kit in ectopic endometrium group was 83.3%. The(++～+++)positive expression rate of C-kit in eutopic endometrium group was 31.2% and in normal endometrium group was 10%.⑥The (++～+++)positive expression of C-kit in endometriosis interna group were higher than endometriosis of ovary group and endometriosis of abdominal group. There were obvious difference compare with other groups (P<0.05).The experimental result indicated:①The (++～+++)positive C-kit expression values were lowest in normal endometrium group, which is 10%.But the expression values was highest in ectopic endometrium group, it is 83.3%. This means potential anti-apoptosis in ectopic endometrium are stronger. So the activeness of endometrium is improved and the capability of blood vessel is improved as well. Both factors are very important to support endometrium to live outside of uterus.Cue: the expression of C-kit play a very important role during the processing of endometriosis and endometriosis interna.②The magnitude of positive expession of C-kit was higher in eutopic endometrium group than normal endometrium group,but there weren't obvious difference in statistics. Cue: the histiooytic bionomics of endometrium weren't difference compare eutopic with normal endometrium.③About etiopathogenisis and pathogenesis of endometriosis interna, there are various kinds of theories, some consider that it is different with EMs, but they all effected by estrogen and pregnancy hormone. Experimental result of discover: C-kit was excessively expressed in ectopic endometrium in adenomyosis. Statistically , There were obvious difference compare with normal endometrium(P<0.05).C-kit correlate with the occurrence and progression of adenomyosis.④Comparing the midle expression of C-kit and strong masculine expression of C-kit, the C-kit values in the endometriosis interna group is higher than ovarian endometriosis and abdominal endometriosis group. And there were obvious difference compare with them(P<0.05). Because the degree of apoptosis may correlate to the activity and expression of C-kit. If the activity and expression of C-kit was lower, the degree of apoptosis would be higher and the activity of endometrium would be lower.According to the experimental result, it was advantage that the ovaries and it's surrounding environment which is very good for endometrium live. It is coincidence[35],that the ectopic endometria were frequent growed in ovares.Conclusions can be drew from the study:①The C-kit was expressed on glandular epithelium of all over endometria,including eutopic and ectopic endometrium in adenomyosis and normal endometrium, but the expressive magnitude weren't differnce. Explanation, there is some close ralationship between the expressive magnatude of C-kit and the implanted potenty of ectopic endometrium.②The expressive magnitude of C-kit weren't obvious difference between proliferative stage and progestational stage in normal and ectopic endometrium group. And it remained the level throughout the menstrual cycle.③C-kit was excessively expressed in ectopic endometrium group, explanation, there is some close relationship between the over expression of C-kit and the occurrence and progression of endometriosis and endometriosis interna. The occurrence and progression of EMs and endometriosis interna are cooperated with many factors and many steps of polygene, many factors are invovled, such as gene breaking,immunology changing,physiological and biochemistry chaging , hormone abnormity adjusting and etc. The over expression of C-kit is only one face of those. To lucubrate C-kit maybe open out the mechanism of EMs and endometriosis interna on the other hand,and can provide the therapy with new tactics .At present, imatinib mesylate(STI571) have been applied to treat tumour patients of C-kit positive expression in foreign clinic, and gain satisfactory therapeutic result. Cue: C-kit are likely to be a new target to treat EMs and endometriosis interna. On the other hand, the degree of apoptosis may correlate to the activity and expression of C-kit, if antisense oligonucleotides be used to interrupt the expression of C-kit gene, and then restart apoptosis , it would inhibit multiplication of endometrial cell. However, current treatment of EMs and endometriois interna still lacked in the view of C-kit gene treatment and clinical observation after medical treating in special purpose. It is expected that internal and foreign scholars lucubrate and practice to accumulate experience and to summarize it.