The Expression And Significance Of Phosphoinositide-3Kinase、cyclinD1、P27、Glycogen Synthase Kinase-3β In Endometrial Intraepithelial Neoplasia And Endometrioid Adenocarcinoma

Objective:Endometrial carcinoma is one of the three common malignant tumors in female genital tract,80%-90%of which are endometrioid adenocarcinoma. Endometrial intraepithelial neoplasia, EIN, is the precancerous lesion of endometrioid adenocarcinoma by the way of monoclonal growing, Separating from endometrial hyperplasia, changing the traditional systematization "endometrial hyperplasia-atypical hyperplasia-endometrioid adenocarcinoma" to "benign endometrial hyperplasia-EIN-endometrioid adenocarcinoma". Phosphatidylinositol3-kinase PI3K/Akt(also known as protein kinase B) is an important cell signal transduction pathway, disordering in a wide range of human tumor spectrum, the mutation of whose compositions is closely related with cell proliferation、apoptosis、cancer transformation and metastasis, etc. This research detected the expression level of PI3K,CyclinDl,GSK-3β，P27and analysed their correlation among proliferation phase endometrium、benign endometrial hyperplasia、EIN and endometrioid adenocarcinoma, exploring the possible mechanism of the downstream molecules of the PI3K/Akt pathway in endometrial precanceous lesions.Method:Reviewed routine HE slices of endometria dilatation and curettage specimens, which were from General Department of Pathology in General Hospital of Tianjin Medical University from2009to2011, then selected10endometrial slices of the proliferation period;15slices of simple endometrial hyperplasia,15slices of complex endometrial hyperplasia, Simple proliferation and complex hyperplasia as a group that was30slices of benign endometrial hyperplasia; Picked out38slices of EIN from the pathological slices with endometrial hyperplasia, which were again reviewed to select30ones; Selected20slices of endometrioid adenocarcinoma. Test the expression level of PI3K、cyclinD1、GSK-3β、P27in each group respectively with immumohistochemistry(IHC) and explore their correlation. The data was analyzed by SPSS16.0software package(Kruskal-WallisH test、Mann-WhitneyU test、Wilcoxon test and Spearman correlation analysis) Results:1. The expression of PI3K was corresponding with the malignant degree. There was a significant difference for the expression of PI3K in each group (p<0.01). The expression of benign proliferative endometrium was higher than proliferation phase endometrium (p<0.01); the expression of EIN was higher than the benign proliferative endometrium (p<0.01); the expression of endometrioid adenocarcinoma was higher than EIN (p<0.01)2. The expression of cyclinDl in endometrioid adenocarcinoma was higher than proliferation phase endometrium、benign proliferative endometrium、EIN (p<0.01).3. The expression of P27in benign proliferative endometrium was lower than proliferation phase endometrium (p<0.05); the expression of EIN was lower than the benign proliferative endometrium (p<0.01); there was no statistic difference of the P27expression between endometrioid adenocarcinoma and EIN (p>0.05).4. There was a significant difference of the GSK-3p cytoplasmic expression in each group (p<0.01), the expression of benign proliferative endometrium was higher than proliferation phase endometrium (p<0.05); the expression of EIN was higher than the benign proliferative endometrium (p<0.01); the expression of endometrioid adenocarcinoma was higher than EIN (p<0.01); the GSK-3P expression in nucleus was on the rise among proliferation phase endometrium、 benign proliferative endometrium、EIN and endometrioid adenocarcinoma,0%、13.33%、36.67%and60%respectively.5. There were obviously positive correlations among the expression of PI3K、 cyclinD1、GSK-3β(p<0.01). P27was negatively correlated with them. PI3K、 cyclinD1、GSK-3β were positively related with age and group(p<0.01), P27was negatively related with age and group(p<0.01).Conclusion:1. The expression of PI3K was corresponding with the malignant degree in the proliferation phase endometrium、benign proliferative endometrium、EIN and endometrioid adenocarcinoma. PI3K may participate in the development and malignant transformation of endometrioid adenocarcinoma.2. CyclinD1was positively correlated with PI3K, the expression of cyclinDl was successively increasing, it was inferred that as the downstream molecule of the PI3K/Akt signal pathway, cyclinDl could promote cell proliferation through PI3K regulation.3. The expression of P27in EIN and endometrioid adenocarcinoma were obviously lower than proliferation phase endometrium and benign endometrial hyperplasia, there was no statistic difference between EIN and endometrioid adenocarcinoma. P27could be an early pathological change of endometrial adenocarcinoma, possibly helpful for an early detection of precancerous lesions.4. The expression of GSK-3beta in endometrioid adenocarcinoma group was higher than other groups, Positive expression located in cytoplasm or nucleus, the cytoplasm expression appeared in each group, there was no nucleus expression in the proliferation phase endometrium, benign hyperplastic endometrium had low quantity expression, the nucleus expression increased in EIN and endometrioid adenocarcinoma, illustrating that nucleus expression could become a signal of cell cancerous change to a certain extent, GSK-3beta may involve in the process of cell proliferation and cancer.5. PI3K, GSK-3beta, cyclinD1were positively correlated with each other, and negatively related with P27, the increasing PI3K expression upregulated GSK-3beta and CyclinD1through the activation of PI3K/Akt signaling pathway, meanwhile made P27inactivated, leading to the cancer. PI3K、GSK-3beta、 cyclinD1and P27protein were the downstream molecules of PI3K/Akt signal pathway, cooperating with each other in the development of endometrioid adenocarcinoma.6. PI3K, GSK-3beta, cyclinD1were positively correlated with age, P27was negatively related with age. With the increasing age, it was more likely to happen for endometrioid adenocarcinom, periodic test may be useful to early detect precancerous lesions.