| BackgroundEndometrial cancer is one of three most common pelvic gynae-cological malignancy, with a2-3%lifetime risk of developing the disease.In2009, Stein discover the MACC1play a role in colon cancer via the HGF-MET pathway. Its expression in tumor specimens is an independent prognostic indicator of metastasis formation and metastasis-free survival. We show that the gene encoding the hepatocyte growth factor (HGF) receptor, MET is a transcriptional target of MACC1. MACC1promotes proliferation,invasion and HGF-induced scattering of colon cancer cells in cell culture and tumor growth and metastasis in mouse models. These phenotypes are lost in cells expressing MACC1mutants lacking the SH3domain or the proline-rich motif.The expressions of MACC1, HGF and C-met in25specimens of normal endometrium tissues,25specimens of simple hyperplasia endometrium tissues,25specimens of atypical hyperplasia endo-metrium tissues, and39specimens of endometrial carcinoma were measured by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). Analyse the relationship between the expressions of MACC1, HGF and C-met and the clinicopathologic features of endometrial carcinoma, also the relationship between the expressions of the three proteins. ObjectiveTest the expressions of MACC1、 HGF、MET mRNA and its encoding protein in the four different types of endometrial tissue by RT-PCR, immunohistochemistry, analyse the difference in the four different types of endometrial tissue, trying to further understand the molecular biology of endometrial carcinogenesis mechanism, seek clinical biomarker benefit for endometrial cancer diagnosis, treatment, to reduce the recurrence rate.Method1. Test the experssions of MACC1mRNA、HGF mRNA、MET mRNA in25specimens of normal endometrium tissues,25specimens of simple hyperplasia endometrium tissues,25specimens of atypical hyperplasia endometrium tissues,and39specimens of endometrial carcinoma by Revers-transcription PCR, and detect the expression difference in the four tissues.2. Test the protein expression of MACC1、 HGF and c-Met in25specimens of normal endometrium tissues,25specimens of simple hyperplasia endometrium tissues,25specimens of atypical hyperplasia endo-metrium tissues,and39specimens of endometrial carcinoma by immunohistochemistry, and detect the expression difference in the four tissues. And explore the relationship of the MACC1、HGF、 c-Met protein with endometrial carcinoma’s clinical pathological fratures.3. Statistical processing:use the SPSS statistical package program17to analyse the datas. The expression of mRNA in different tissues were tested by One-way analysis of variance (by the normality test and homogeneity of variance test). The difference between two groups was tested by the LSD test.The enumeration data was analyzed by Fishercorrect test. The correlation analysis was tested by Spearson rank correlation coefficient test. Significant level is a=0.05.Results1. In normal endometrial tissue, simple hyperplasia endometrium tissue, atypical hyperplasia of endometrium and endometrial carcinoma tissue, the expression level of MACC1mRNA is0.015±0.051.0.019±0.061、0.042±0.050、0.216±0.062 respectively, The expression level of HGF mRNA is0.021±0.034、0.023±0.026、0.043±0.038、0.134±0.054respectively, The expression level of MET mRNA is0.023±0.041、0.025±0.042、0.103±0.054、0.172±0.044respectively.2. Through statistical analysis, relative expression level of MACC1mRNA in four types of endometrial tissue are different, and it has statistical significance (F=13.524, P=0.000<0.05). The relative expression of MACC1mRNA in endometrial cancer tissue was obviously higher than that in atypical hyperplasia, simple hyperplasia and normal endometrium tissues, they have statistical significance (P1=0001, P2=0.001, P3=0.001, P<0.008), The differences between typical hyperplasia and simple hyperplasia group, atypical hyperplasia and normal endometrium group, normal and simple hyperplasia group, there have no statistically significant difference (P1=0.934, P2=0.670, P3=0.731,all P>0.008)3. Through statistical analysis, relative expression level of HGF mRNA in four types of endometrial tissue are different, and it has statistical significance (F=17.59, P=0.017<0.05). The relative expression of HGF mRNA in endometrial cancer tissue was obviously higher than that in atypical hyperplasia, simple hyperplasia and normal endometrium tissues, they have statistical significance (Pi=000, P2=0.000, P3=0.0075, P<0.008),The differences between typical hyperplasia and simple hyperplasia group, atypical hyperplasia and normal endometrium group, normal and simple hyperplasia group, there have no statistically significant difference (P1=1.000, P2=0.76, P3=0.890, all P>0.008)4. Through statistical analysis, relative expression level of MET mRNA in four types of endometrial tissue are different, and it has statistical significance (F=14.65, P=0.021<0.05). The relative expression of MET mRNA in endometrial cancer tissue was obviously higher than that in atypical hyperplasia, simple hyperplasia and normal endometrium tissues, they have statistical significance (P1=0001, P2=0.000, P3=0.005, P<0.008),The differences between typical hyperplasia and simple hyperplasia group, atypical hyperplasia and normal endometrium group, normal and simple hyperplasia group, there have no statistically significant difference (P1=0.974, P2=0.859, P3=0.627, all P>0.008)5. In normal endometrial tissue, simple hyperplasia endometrium tissue, atypical hyperplasia of endometrium and endometrial carcinoma tissue, the positive rate of MACC1protein were8.0%,12.0%,36.0%,12.0%respectively, HGF protein positive rate respectively is4.0%,8.0%,32.0%,8.0%, c-Met protein positive rate were8.0%,16.0%,44.0%and16.0%respectively.6. The positive expression rate of MACC1protein in endometrial carcinoma tissue was significantly higher than it in simple hyperplasia and normal endometrium tissues, the differences have statistical significance (P1=0.000, P2=0.000, P<0.008), but have no statistically significant with atypical hyperplasia group(P=0.028>0.008). Between atypical hyperplasia and normal endometrium group, atypical hyperplasia and endometrial simple group, the simple hyperplasia and normal endometrium tissues, there have no statistically significant difference (P1=0.047, P2=0.017, P3=1.000, P>0.008).7. The positive expression rate of HGF protein in endometrial carcinoma tissue was significantly higher than it in simple hyperplasia and normal endometrium tissues, the differences have statistical significance (P1=0.000, P2=0.000, P<0.008), but have no statistically significant with atypical hyperplasia group(P=0.0281>0.008). Between atypical hyperplasia and normal endometrium group, atypical hyperplasia and endometrial simple group, the simple hyperplasia and normal endometrium tissues, there have no statistically significant difference (P1=0.034, P2=0.010, P3=1.000, P>0.008).8. The positive expression rate of c-Met protein in endometrial carcinoma tissue was significantly higher than it in simple hyperplasia and normal endometrium tissues, the differences have statistical significance (P1=0.000, P2=0.000, P<0.008), but have no statistically significant with atypical hyperplasia group(P=0.045>0.008). Between atypical hyperplasia and normal endometrium group, the difference was statistically significant (P=0.004<0.008), Between atypical hyperplasia and endometrial simple group, the simple hyperplasia and normal endometrium tissues, there have no statistically significant difference (P1=0.031,P2=0.663, P>0.008).9. MACC1protein positive expression rate is closely related to the clinical stage of endometrial carcinoma (P=0.002), muscular infiltration depth (P=0.024) and the presence of lymph node metastasis (P=0.013), but has nothing to do with the patient’s age, cell differentiation level and presence of recurrence.10. HGF protein positive expression rate is closely related to the clinical stage of endometrial carcinoma (P=0.001), muscular infiltration depth (P=0.001) and the presence of lymph node metastasis (P=0.045), but has nothing to do with the patient’s age, cell differentiation level and presence of recurrence.11. C-Met protein positive expression rate is closely related to the clinical stage of endometrial carcinoma (P=0.001), muscular infiltration depth (P=0.001) and the presence of lymph node metastasis (P=0.045), but has nothing to do with the patient’s age, cell differentiation level and presence of recurrence.12. The expression of MACC1protein was positive correlated with the HGF and c-Met respectively(r=0.525, P=0.000; r=0.393, P=0.008), The expression of HGF protein was positive correlated with the c-Met (r=0.334, P=0.027).Conclusion1. MACC1、HGF、c-Met may involved in the malignant transformation of endometrial carcinoma.2. The MACC1protein is associated with the malignant degree of carcinoma of endometrium via the HGF/c-Met signal transduction pathway. |
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