The Expression And Clinical Significance Of Pl6^INK4a And PCNA In Endometrioid Adenocarcinoma

Purpose: Study of p16^INK4aand PCNA protein in endometrioidadenocarcinoma and its clinical significance of the expression of, to furtherexplore the endometrioid adenocarcinoma of the occurrence, the developmentprocess, which aims to provide some new approaches to clinical diagnosis andtreatment.Endometrioid adenocarcinoma （Endometrioid adenocarcinoma, EA） isthe female reproductive system is one of the most common malignant tumors.In recent years, along with test technology development, people on endometrialcancer pathological mechanism has further understanding, multiple geneticalterations and EA related, exploration of oncogene and tumor suppressor geneand endometrial carcinoma, bound for endometrioid adenocarcinoma of thebiological characteristics of assessment and targeted gene therapy for findingnew molecular biological indicator. PCNA as a non histone nuclear protein,eukaryotic replication complex core component, has a special ring three levelstructure. As a eukaryotic DNA polymerase delta drive factor, with differentreplication associated protein binding, coordination of DNA replication process.At the same time, PCNA also functions as a conversion factor, through differentcontrol mode and multiple roles of cytokines, involved in DNA damage repair,cell cycle regulation and apoptosis of many important cellular events. Inaddition as the cell proliferation index, PCNA and tumor cell proliferativedisease occurrence and Development Association, therefore in clinical onPCNA in-depth study has important significance. p16^INK4ais a cyclin-dependentkinase inhibitor, as multiple tumor suppressor factor family member, in thefield of molecular biology and tumor related research is more, about75%more than the human malignant tumors occur p16^INK4agene deletion, mutation,abnormal gene silencing or protein functional deactivation, it is frequencyexceeds PCNA in a variety of tumors in change. p16^INK4ais involved in tumourformation and development mainly through the regulation of the cell cyclecheckpoint, the cell cycle arrest in G phase to enter S phase. Recent studiesshowed that, p16transcript variants of p16^INK4ain addition to above, with majorbiological functions, but also with other cellular processes, such as cell agingand cell self-renewal. p16^INK4aexpression increased or enhanced activity insenescent cells decreased function of role; and decreased p16^INK4aactivity canbe significantly enhanced cell proliferation and the ability to update.The experimental detection of p16^INK4aand PCNA protein in20cases ofnormal endometrium （A），15cases of proliferative phase endometrium （B），15cases of complex hyperplasia endometrium（C），20cases of atypicalhyperplasia of endometrium （D） and40cases of endometrioid adenocarcinoma（F） expression in tissue specimens，all endometrial cancer tissue specimenswere endometrioid adenocarcinoma of the uterus, membranous adenocar-cinoma according to degree of malignancy and prognosis were divided into twogroups:（1） histological grade: G1+G2group, G3group （G1and G2cases.G3relatively less, so G1and G2cases and comparison with G3）; operationpathologic staging: I^II and III^IV group （II, III stage by stage and IV stagewere few, so I^II total number of cases with III^IV phase comparison）.（2）the depth of myometrial invasion>1/2and invasion depth is less than or equalto1/2groups; lymph node，metastasis free group. Analysis of two kinds ofprotein in different tissues of expression differences and relevance， aims toprobe into the two in endometrioid adenocarcinoma of the expression andtumor clinical pathological factors and relationship between the two in tumorprogression, metastasis in relation to each other. Thus for endometrioidadenocarcinoma diagnosis, targeting gene therapy provides a new train of thought.Methods: Randomly selected Beijing China-Japan Friendship Hospitalfrom March2010～July2011operation excision of endometrial pathology inarchival paraffin specimens from a total of110cases. All specimens are in thefresh material, immediately by10%neutral formalin fixed, paraffin embedded.Serial sections of4Mm thick, in each case of the preparation of3, respectively,HE staining, immunohistochemical staining, reagent box known positive filmwas used as a positive control, all sections were confirmed by pathologyexperts blind identification, in order to detect PCNA and p16^INK4aexpression.Application of data statistics and analysis to SPSS17.0, P <0.05as there weresignificant differences.Results:1、PCNA in cell nuclei appear brown granules for positive signals.Staining positive score over5points to8points. In group A, group B, group C,group D, group E. The positive expression of PCNA protein were20%，20%，27%，40%and73%. PCNA in endometrioid adenocarcinoma tissues wassignificantly higher than that in normal endometrium, simple hyperplasia,complex hyperplasia and atypical hyperplasia endometrium （χ²=12.79, χ²=14.37, χ²=9.54, χ²=5.95, P <0.05）. But in normal endometrium andendometrial hyperplasia period （including simple and complex hyperplasiahyperplasia of endometrium） and atypical hyperplasia endometrium expressioncompared with no significant difference between. In endometrioidadenocarcinoma tissues:（1） and tumor malignancy related: the positive rate ofPCNA protein expression and EA grading was significantly related tohistological grade, G3PCNA protein expression was significantly higher thanthat in group G1+G2（χ²=4.71, P <0.05）; operation-pathologic staging of III^IV organization the positive expression of PCNA was significantly higherthan that of I^II endometrioid adenocarcinoma tissue （χ²=4.40, P <0.05）.（2） associated with prognosis: the depth of myometrial invasion>1/2of PCNAprotein expression in depth less than or equal to1/2was significantly higherthan that of the expression （χ²=4.40, P <0.05）; and if no significant correlationwith lymph node metastasis （χ²=0.47, P>0.05）.2、The expression of p16^INK4aproducts mainly in the nucleus appear brown,staining positive expression. Expression of positive score over4points to6points. From group A, group B, group C, group D to group E, the positiveexpression of p16^INK4aprotein were70%,40%,40%,33%,20%. p16^INK4aproteinin normal endometrial tissue expression was significantly higher than that ofsimple hyperplasia, complex hyperplasia, atypical hyperplasia endometrium,endometrial adenocarcinoma tissue （χ²=12.79, χ²=14.37, χ²=9.54, χ²=5.95, P<0.05）. The p16^INK4aprotein in simple hyperplasia endometrial tissue in thedeletion rate expression was significantly higher than that of atypicalhyperplasia of endometrium, endometrial adenocarcinoma tissues （P <0.05）,while the remaining three group comparison between groups was notstatistically significant （χ²=2.915, P>0.05）. In endometrioid adenocarcinomatissues:（1） and tumor malignancy related: in G3positive expression of p16^INK4aprotein was significantly lower than that of group G1+G2（χ²=6.23, P <0.05）;clinical stage III-IV in tissues of positive expression of p16^INK4aprotein wassignificantly lower than that of stage I-II endometrial carcinoma （χ²=5.4, P <0.05）.（2） associated with prognosis: the depth of myometrial invasion>1/2ofp16^INK4aprotein expression in significantly less than the depth of less than1/2of the expression （χ²=2.62, P <0.05）; from the lymph node metastasis, nolymph node metastasis in carcinoma of the positive expression rate of p16^INK4a（46.2%） was higher than that of lymph node metastasis of cancer tissue （25%）,no significant differences （χ²=1.03, P>0.05）.3、statistical results showed that the expression of p16^INK4aand PCNA inendometrioid adenocarcinoma was negatively correlated （r=-0.061, P <0.05）. Conclusion:1、The expression of PCNA protein in EA significantly higher than that innormal endometrium, endometrium and atypical hyperplasia of theendometrium, suggesting that PCNA may promote the occurrence ofendometrial adenocarcinoma development.2、Of PCNA expression in poorly differentiated endometrial adenocar-cinoma, surgical-pathologic stage advanced, depth of myometrial invasion>1/2endometrial adenocarcinoma was significantly increased. The highexpression of PCNA in the EA may indicate a high degree of malignancy andpoor prognosis.3、p16^INK4agene expression in EA was significantly lower than that innormal endometrium, proliferative phase endometrium and atypical hyperplasiaendometrium, suggesting that p16^INK4agene deletion may be the cause ofendometrioid adenocarcinoma occurs, the development of a cause.4、The role played by p16^INK4athe loss of expression of endometrialadenocarcinoma surgical-pathological stage late histological grade wassignificantly related to poor differentiation and depth of myometrial invasion.Its low expression may indicate the degree of malignancy and poor prognosis.5、Through the p16^INK4aand PCNA joint detection is expected toovercome single detection sensitivity, accuracy is low, can be more true,reliable response to tumor occurrence, development, contribute to the EAdiagnosis, therapy and prognosis.