The Primary Research Of The Expression And Significance Of Pin1 And CyclinD1 In Endometrial Carcinoma

ObjectiveEndometrial cancers(EC)is the malignant tumor arising from Endometrial epithelial cell,is one of the most common female reproductive system tumor,and have a high incidence in perimenopausal and postmenopausal women.EC has a large number of new cases every year,and its incidence is rising trend year by year,is a common gynecologic malignant tumors of the third death.The occurrence,development and metastasis of Endometrial cancer is a complex process,involing multiple factors and multi-stage process,its occurrence and development are the result of a variety of factors,genetic effect,may involve the regulation disorder of multiple signal transduction pathways,multiple oncogenes and tumor suppressor gene,is a quite complex process.Pin1 is a family member of peptidyl proline cis/trans isomerase(PPIases),it can adjust the cis\trans isomerization of proteins so that can influence the catalytic activity of enzymes,protein stability,the interaction between protein and subcellular transportation,and other functions.The disor-der of pin1 has confirmed that is related to many pathological processes,including immune response,aging,cell apoptosis,alzheimer's disease,and many kinds of cancer.There is a high expression of pin1 in a series of cancer,such as esophageal squamous cell carcinoma(ESCC),cervical cancer,ovarian cancer,breast cancer,lung cancer,and prostate cancer and so on,and it is generally accepted that Pin1 is a marker of poor prognosis.It is already clear that CyclinD1 is related to the development and occurrence of human cancer.CCND1 is a human oncogene exist extensively and have a high level expression in breast,lung,melanoma,and oral squamous malignant tumor cell.Human cancer and cancer development is often due to the disorder of CCND1 gene in cell cycle regulation.Pinl is excessive expressed in a variety of human and animals tumor,and can promote the overexpression of CyclinD1,a downstream genes of pin1,through at least three ways,resulting cell metabolic abnormalities,excessive proliferation,cycle disorders,and even the occurance of cancer.This study is through immunohistochemical method SABC to detect the expression of Pin1 and CyclinD1 in endometrial carcinoma(EC)and normal endometrium(NE),and to study the correlation between the expresseion in endometrium of Pin1 and CyclinD1.Material and Method:The cases used in this study are from Tai'an City central hospital between January2013 and June 2015.These 42 cases of endometrial carcinoma,including 31 cases of adenocarcinoma,8 cases of adenocarcinoma with phosphating,3 cases of serous papillary adenocarcinoma;19 cases of stage I,14 of II,9 of III-IV,are surgical treated,and clinical data is complete,the diagnosis is clear,the specimen is complete,and no preoperative chemotherapy.Specimens of 42 cases involve 24 cases(57.14%)of myometrium invasion in half or less,and 18 cases(42.86%)myometrium invasion over 1/2;5 cases of lymph node metastasis,accounting for 11.90%,37 cases of no lymph node metastasis,accounting for 88.10%.Another 10 cases of other benign gynecological diseases,which is surgicaly remove the uterus(such as uterine fibroids,etc.),and take the endometrium as control group.All dyed section is read by double blind method by two experienced pathology doctors under the same conditions,using optical microscope.The expression of Pinl and CyclinD1 in normal endometrium and endometrial carcinoma,is detected by immunohistochemical SABC method in endometrium and endometrial carcinoma.The result:(1)The expression of Pinl in endometrial carcinoma:The expression of Pinl in endometrial carcinoma is in cell nucleus and(or)cytoplasm,partial Cytoplasmic membrane is coloured with yellowish-brown granules,or cytoplasm contains scattered or concentrated brown granules(figure 3).The experiment shows that there are no high level expression of pin 1 in 10 cases of normal endometrium.In endometrial carcinoma the rate of high pin1 expression is 54.76%,significantly higher than that of normal endometrium,statistical differences excists between the two groups(x~2=6.512,P=0.014)(Table 2)?There was no significant correlation between overexpression of Pinl with the age,menopausal status,histology,pathologic stage,lymph node metastases,etc.,and were positively correlated to the clinical stages(x ~2=8.922,P=0.030).(2)The expression of CyclinDl in endometrial carcinoma:The expression of CyclinD1 in endometrial cancer cells is mainly in the nucleus,and part of the expression in the cytoplasm(figure 9).In the endometrial tissue of uterine benign lesions,CyclinD1 protein expression rate is 10%;In endometrial carcinoma tissues,CyclinD1 protein expression rate is 42.86%.CyclinD1 expression in endometrial cancer was significantly higher than those of normal endometrium,there was a significant difference between the two groups,the difference has statistical significance(x~2=6.555,P=6.555)(table 5).The expression of CyclinD1 is positively correlated with the clinical stages(x~2=11.559,P=0.009),and there was no obviously correlation with the patient's age,menopausal status,histology,pathologic stage,lymph node metastases,etc.(3)The expression of Pinl and CyclinD1 in endometrial cancer cells:23 cases of endometrial cancer that Pinl is overexpressed cotain 15 cases of cyclinD1expression positively,the rate is 65.22%;19 cases of endometrial cancer that Pinl is lowexpressed cotain only 3 cases of cyclinD1 expression positively,the positive rate of15.79%.In the endometrial tissue,which pin1 is over expressed,the rate of cyclin Dl positive expression increased significantly;the expression of pin1 and CyclinD1 in endometrial cancer is significant positive correlation(x~2=10.380,P=0.001;r=0.497,P=0.001).(table 8)Conclusion:(1)The expression of Pin1 in endometrial cancer was significantly higher than in normal endometrium,and the difference is statistically significant.The expression of CyclinD1 in endometrial cancer was significantly higher than in normal endometrium,and the difference is statistically significant.(2)There was no significant correlation between the expression of Pin1 in endometrial cancer with patient?s age,menopausal status,histology,pathologic stage and lymph node metastasis,the expression of Pin1 in endometrial cancer is positively correlated to the clinical stages.There was no significant correlation between the expression of CyclinD1 in endometrial cancer with patient?s age,menopausal status,histology,pathologic stage and lymph node metastasis,the expression of CyclinD1 in endometrial cancer is positively correlated to the clinical stages.(3)The expression of pin1 in endometrial cancer is positively correlated with cyclinD1,high level expression of Pinl may improve the expression of CyclinD1,Pinl may be a upper control factor of CyclinD1.The abnormal expression of pin1 and CyclinD1 may jointly participate in the occurrence and development of endometrial carcinoma.