Expression And Clinical Significance Of ERK1/2 And MMP-9 In Human Cholangiocarcinoma

Introduction and ObjectiveThe cholangiocarcinoma is a common malignant tumor. The symptoms appearslate, the early diagnosis is difficult, and the rate of surgically radical excision is low, so the prognosis is bad. Therefore, investigation of the mechanism and finding theeffective therapeutic method are important to elevate the diagnosis and treatment ofthe cholangiocarcinoma.Of the various families of MAPKs, which are also referred to as extracellularsignal-regulated kinases (ERKs), the first to be characterized were ERK1 and ERK2.Both of these ERKs are activated in response to diverse extracellular stimuli and byprotooncogene-encoded proteins that induce proliferation. A cascade ofphosphorylation events downstream from Ras activates these kinases. Upstreamregulation of the MAP kinase pathway is complex as evidenced by the number offunctions fulfilled by its activation.ERK has been the best characterized and is more pertinent to aberrant signalingin human cancer. ERK has been the best characterized and is more pertinent toaberrant signaling in human cancer. The ability of cancer cells to invade other tissuesand spread to distant organs is an often-fatal characteristic of malignant tumours.Although the mechanistic process of ECM degradation mediated by MMPs had beenthe focus of many investigations for years, recent studies have shown that the role ofMMPs in cancer progression is much more complex than that derived from theirdirect degradative action on ECM components. In current study, immunologic histochemistry methods was used to investigate the expression of ERK1/2 andMMP-9 in cholangiocarcinoma, reveal the relationship of the two proteins incholangiocarcinoma and whether existing correlation between of them.MethodsThe 50 specimens of cholangiocarcinoma were selected from January, 1999 toDecember, 2005 at the First Hospital of China Medical University, and allpathologically validated. Para-tumor tissue of biliary tract was from 31 cases ofradical excision, and no tumor cells were found pathologically. We detected theexpression of TLR4 and HSP70 in the tumor and para-tumor tissue in immunologichistochemistry methods, and utilized the image analysis software (Image-pro Plus 5.0)to count and analysis the specimens. Statistic analysis was completed with statisticsoftware SPSS11.0, and K-S test, analysis of variance, SNK test and t test wereused.The analysis of correlation of each factor used linear correlation. P＜0.05, was asthe level for statistical significance.RESULTSERK1/2 and MMP-9 were mainly expressed on cytoplasm. The expression ofERK1/2 and MMP-9 was significantly higher in cholangiocarcinoma tissue than inpara-tumor tissue (P＜0.05). Further study indicated the expression of ERK1/2 andMMP-9 had close relationship with the initiation and development ofcholangiocarcinoma, yet had no relationship with age, sex, and TNM classification(P＞0.05). The expression of ERK1/2 and MMP-9 has no significant correlation.ConclusionThe expression of ERK1/2 and MMP-9 in the tumor tissue was higher than thatin the para-tumor tissue. But the expression of ERK1/2 and MMP-9 were highlycorrelated with the pathologic differetiation degree of turner, the lower differetiationdegree, the more expression, but had no relationship with the age, sex, and TNMclassification, The correlation analysis of the expression of ERK1/2 and MMP-9revealed that there was no relationship between them.