The Relationship Of HGF, C-Met And MMP-2 With The Pathogenesis Of Endometriosis

Objective To investigate the relationship and clinical significance of hepatocyte growth factor (HGF ), its receptor ( c-Met) and matrix metalloproteinase-2 ( MMP-2 ) with the pathogenesis of pelvic endometriosis.Methods The Streptavidin-Peroxidase ( S-P ) immunohistochemical method was used to detect the immunoexpression of HGF, c-Met and MMP-2 in the eutopic endometrium of forty five women with pelvic endometriosis (endometriosis group: according to menstrual cycle, twenty cases'endometrium in proliferative phase and twenty five cases'endometrium in secretive phase) and thirty women without endometriosis ( control group: twelve cases'endometrium in proliferative phase and eighteen cases'endometrium in secretive phase respectively, according to menstrual cycle ).Results1. Immunostaining of HGF, c-Met and MMP-2 was localized in both the cytoplasm and cell membrane of glandular epithelial cells and stroma cells of the eutopic endometrium. Yellow brown granula was positive immunoexpression.2. To detect the light intensity of HGF, c-Met and MMP-2.(1) The light intensity of these markers in the eutopic endometrium of women with pelvic endometriosis ( HGF 0.163 + 0.009, c-Met 0.163 + 0.010, MMP-2 0.162 ± 0.009 ) was all significantly higher than that of control group ( HGF 0.156+0.013, c-Met 0.154+0.011, MMP-2 0.156+0.011 ). There were significant differences ( all P -value < 0.01).(2) According to menstrual cycle, there were apparent variations detected in the immunoexpression of these markers in the eutopic endometrium of women regardless of the presence of endometriosis. The light intensity of these markers in the secretive endometrium of women with pelvic endometriosis was markedly higher ( HGF 0.167 + 0.009, c-Met 0.167+0.009, MMP-2 0.166 + 0.009 ) than that in the corresponding proliferative endometrium ( HGF 0.159+0.009, c-Met 0.159+0.010, MMP-2 0.158+ 0.007 ). The significant differences were observed ( HGF P-value < 0.01, c-MetP-value < 0.05, MMP-2 P-value < 0.01 ). The same results were found in the control group. The light intensity of these markers was higher in the secretive endometrium ( HGF 0.160+0.012, c-Met 0.158+0.009, MMP-2 0.160+0.009 ) than that in the proliferative endometrium ( HGF0.149±0.012, c-Met 0.149+0.011, MMP-2 0.150+ 0.009 ). The differences were statistically significant too ( HGF P-value < 0.05, c-Met P-value < 0.05, MMP-2 lvalue < 0.01 ).(3) In our study, We also observed a significant increase in the immunoexpress-ion of these markers in the eutopic endometrium of women with pelvic endometriosis whether in the proliferative endometrium or secretive endometrium as opposed to the control group respectively. The differences between the two groups were statistically significant also ( HGF P-value < 0.05, c-Met P-value < 0.05 and MMP-2 P-value= 0.01 in the proliferative endometrium respectively; HGF P-value < 0.05, c-Met P-value < 0.01 and MMP-2 P-value < 0.05 in the secretive endometrium respectively ).3. To explore the correlation of HGF, c-Met and MMP-2 each other.Positive correlations were observed among the immunoexpression of these markers in the endometrium of women with and without endometriosis ( HGF and c-Met r=0.945, c-Met and MMP-2 r=0.885, HGF and MMP-2 r=0.902 in the endometriosis group respectively, all P-value < 0.01; HGF and c-Met r=0.945, c-Met and MMP-2 r—0.937, HGF and MMP-2 r—0.949 in the control group respectively, all P-value < 0.01).Conclusion1. These markers ( including HGF, c-Met and MMP-2 ) in the eutopic endometrium of women may be involved in the normal menstrual cycle by endometrium destruction and reconstruction whether or no endometriosis.2. These markers may play an important role in the pathogenesis of endometriosis The overexpression of these markers in the eutopic endometrium of women with endometriosis was essentially responsible for the pathogenesis of endometriosis. In a manner analogous to tumour metastasis and invasive mechanism. On the one hand, HGF/c-Met may play a crucial role by independently cell proliferation, cell differentiation, migration, invasion, angiopoiesis and implantation. On the other hand, HGF/c-Met may increase the level of MMP-2 in the endometrial cell and so MMP-2 mediated endometrial tissue turnover during menstruation-appear to be involved in thisinvasive process by degradation of extracellular matrix ( ECM ). Up-regulation of HGF, c-Met and MMP-2 may cooperatively contribute to survival and development of endometriosis.3. To study the role of these markers in the pathogenesis of pelvic endometriosis may also offer a new theory of endometriosis and help in selecting the optimal treatment methods.