| IntroductionEndometrial carcinoma is one of the most common pelvic genital cancer in women , and the incidence of this disease has continued to increase since 1980s . Although the exact cause of endometrial carcinoma remains unknown , the perennial estrogenic effects on the endometrium , without antagonism of progestin , may play an important role for the great cases of endometrial carcinoma . Recently , the investigation into the etiology of endometrial carcinoma is being concentrated in E , ER and three kinds of genes ( oncogene , tumor suppressor gene , DNA repairing gene ) and their relationship .Pituitary tumor - transforming gene (PTTG) recently cloned from human testis is a novel potent oncogene that is expressed in most tumors . Overexpres-sion of PTTG in NIH 3T3 cells induces cell transformation in vitro, and promotes tumor formation in vivo . PTTG possesses transactivation ability, is involved in tumor angiogenesis and maintenance of chromosome stability , and participates in tumorigenesis though its overexpression . Increased expression of PTTG has been reported in several human tumors , including those of the breast , ovary , and liver etc , and was related to their clinical - pathological characteristic such as pathological subtype, surgical — pathological stage , tumor metastasis and so on . Oncogene c - myc is a NP gene , and can be activated by gene amplification and overexpression . C - myc was identified as a major target gene for PTTG in HeLa S3 cells , and PTTG is involved in cellular transformation and tumorigenesis through activation of c - myc oncogene.The objective of this study was to examine the expression of PTTG protein and c - myc protein in normal endometrial tissue , atypical hyperplasia endome-trium and endometrial carcinoma by immunohistochemistry and Western blot respectively , to investigate the correlation and significance of them in tumorigenic process of endometrial carcinoma , and whether the level of PTTG protein could vary with the clinical - pathological characteristic of endometrial carcinoma .Materials and methods48 cases of endometrial carcinoma , 11 cases of atypical hyperplasia endo-metrium and 18 cases of normal endometrial tissue was enrolled from the O&G ward of the second affiliated hospital of China Medical University . All the patients were not treated by chemotherapy , radiotherapy and sex hormone therapy before operation . One part of the surgically resected specimens were fixed with 10% formalin , paraffin embedded , and serially sectioned for histopathological diagnosis. Another part of the specimens were frozen at - 80X!. Immunohistochemistry (PV - 9000 polymer detection system) was applied to determined the expression rate of PTTG protein and c - myc protein , and Western blot was applied to determined the semi — quantitated expression of them . The data was analyzed by SPSS 11.5 statistical software . The x2test , t test , one - way ANOVA , linear correlation were used for the statistics , p <0.05 was considered significant .ResultPTTG protein and c - myc protein were mainly localized in plasma of glandular epithelium of endometrium , and partially localized in nucleus of glandular epithelium of endometrium . The expression rate and average quantity of PTTG protein and c -myc protein (66.7% ,131. 1458 ±77. 5667;52. 1% 101. 1458 ±81.5728 respectively) in endometrial carcinoma was significantly higher than those in atypical hyperplasia endometrium (36.4% ,37. 1818 ±42. 4966;27. 3% , 27.2727 ±40.4321 respectively) and normal endometrial tissue (16. 7% ,11. 2222 ±22. 8385;11. 1% 9.6067 ± 19.7067 respectively ) . The difference were significant among those three groups (p <0.05) .The expression of PTTG protein was related to surgical - pathological stage , with the lesions progressed from I —> II —? HI - IV stage , a increasing tendency of PTTG expression was observed , The expression rate and average quantity of PTTG protein were 52.0% , 85.4800 ±48. 9354;66.7% 139. 6667 ±73. 1540;92.9% ,220.0714 ±40.2367 respectively . The difference were significant among those three groups ( p <0.05) . High level expression of PTTG protein was significantly related to myometrial infiltration depth and lymphatic metastasis (p<0.05 , respectively) . The expression of PTTG protein was irrelevant to patients'age and pathological subtype (p >0.05 , respectively).The expression rate of c - myc protein in tissues with PTTG protein coexpression (58. 3% ) was higher than in those without PTTG protein coexpression (30.4% , p <0.05) .A positive correlation was observed between PTTG protein and c - myc protein ( r = 0.603 ,p <0.01).DiscussionThis study has demonstrated that the expression rate and average quantity of PTTG protein and c - myc protein were elevated in atypical hyperplasia endome-trium in comparison with those in normal endometrial tissue , and even further increased in endometrial carcinoma;the expression of PTTG protein was related to surgical - pathological stage , myometrial infiltration depth and lymphatic metastasis;a positive correlation was observed between PTTG protein and c - myc protein . This results suggest that the overexpression of PTTG protein promotes the endometrial cellular proliferation and induces malignant transformation through activation of c - myc oncogene, and is involved in pathogenesis of endometrial carcinoma .Although the pathogenesis of endometrial carcinoma still remains unclear , most of scholars support that the long - term estrogenic effects on the endometri-um is associated with endometrial hyperplasia , even carcinomatous change . The study that estrogen induced PTTGmRNA in rat pituitary GH3 cells in vitro by Hong Yin et al indicates that estrogen may induce tumorigenesis of endometri-um through up - regulating the expression of PTTG gene ( encoding PTTG pro-tein of 22KDa ) . PTTG protein has a transcriptional activation function , with the study of Lin Pei et al , c - myc is its major downstream target gene . PTTG protein binds to c — myc promoter near the transcription initiation site in a protein complex containing the USF1 . Many tests show that overexpression of c -myc protein stimulates cell cycle progression , causes transformation , blocks differentiation , induces apoptosis , and has a close relationship with the onset and development of endometrial carcinoma . Our investigations that the association of PTTG protein expression with the pathological course of endometrial carcinoma , and the correlation of PTTG protein and c - myc protein in endometrial carcinoma are in agreement with these basal researches mentioned above .Moreover , the test that the expression of PTTG protein was related to surgical - pathological stage , myometrial infiltration depth and lymphatic metastasis in endometrial carcinoma indicates PTTG may become a novel marker of endometrial carcinoma .ConclusionThe overexpression of PTTG protein and its correlation with surgical — pathological stage , myometrial infiltration depth and lymphatic metastasis in endometrial carcinoma indicates that up — regulated PTTG protein involves in the path-ogenesis of endometrial carcinoma .The overexpression of c - myc protein in endometrial carcinoma indicates that it plays an important role in the onset and development of endometrial carcinoma.The positive correlation of PTTG protein and c - myc protein indicates that PTTG protein is involved in tumorigenesis of endometrium through activation of c - myc oncogene.
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