Expression And Clinical Significance Of PCNA,CD34 And P-gp In Osteosarcoma

Objective:Osteosarcoma is usual in primary malignant tumor of bo-ne in teenager,which cause different levels of drug resistance in chemot-herapy in recent research.Surgical removal of the tumor is the most im-portant part of comprehensive treatment in osteosarcoma,and chemothera-py has been the most important means of adjuvant therapy.Chemotherap-eutics can not only kill the remaining cancer cells or its metastases,butalso is effective for control of recurrence.The cause of death inpatinentswith osteosarcoma was multiple drug resistance leading to lung metasta-sis by clinical observation and literature.There is Widespread attention onmulti-drug resistant mediated by MDR-1/P-gp to treatment effect.Mecha-nism of multiple drug resistance on the basis of the MDR-1/P-gp is a hot- spot research.P-g P,a membrane glycoprotein,is encoded by multiple drug resistance(MDR) gene,which decompose ATP to pumpdrugs out of cells, reducing to killing effect of the drug.But P-gp expressing is not peculiar in tumor cells,there is different levels of expression in normal tissues,mainly in some secretion and excretion function of tissues or organs.P- glycoprotein pathologically can excrete the drugs within the tumor cells,which mediates the generation of tumor MDR,and physiologically reduceexogenous toxins absorbed by tissue cells,so as to protect the body.It c-ould also be the reason that some cancer initially is not sensitive to ch-emotherapy.MDR reversal agents mediated by P-gp are earlier,and wides-pread reversing MDR’s strategy,which is also one of research hotspot in the study of treatment of osteosarcoma.In addition,P-gp is related to thedrug resistance of osteosarcoma and MDR-1 gene expression,cell signali-ng pathways,immune and other aspects.Therefore,research on P-glycoprot-ein in malignant tumor has reached a white-hot stage.Proliferating Cell Nuclear Antigen(PCNA) is on behalf of tumor cell proliferateion rate,can be evaluated in the curative effect of chemotherapy.PCNA antisense oligo-nucleotide,a newly developed drug,inhibitit the proliferation of geneticm-aterial in the nuclei in it in genen.PCNA as molecular targets of antise-nse nucleic acid treatment,inhibition of PCNA gene expression,stop theproliferation or cell inadormant state.Technology to inhibit the expression of PCNA gene antisense,inhibit tumor cell proliferation,and little impact onnormal cells.CD34,a kind of adhesion molecules,expressed in endothelio-cyte,plays an important role in adhesion.It is marked in microvessel de-nsity to calculate MVD and to assess tumor blood supply and also inv-olved in proliferation,differentiation and metastasis,which is closely relat-ed to the development of tumor metastasis.Tumor growth and metastasisneed nutrients from the blood supply and blood vessel is an important reason for tumor formation.Tumor angiogenesis inhibitors is easier to re-ach the target cells,play the role of its resistance to blood vessel formation andso on,and not easy to produce drug resistance,week toxi effect. It, with combination of chemotherapy drug,can improve the effect of conventionalchemotherapy.The inhibitors in blood vessels,inhibit angiogenesisor prom-ote endothelial cell apoptosis,metastases in a stationary state,inhibit tumor recurrence and metastasis.Due to the antitumor angiogenesis,gene therapy isnot affected by the tumor cell cycle,Which is a good complement other treatment options.At present a lot of experimental demonstration,P-glyco-protein,PCNA and CD34 in bone sarcomawith high expression,and as a target protein in tumor cells in cancer treatment have beenobtained in theprocess of objective curativeeffect.But is there relation between multidr-ug resistance and proliferation?And is it involved in angiogenesis?Dome-stic reports are few and controversial.We selected 51 cases of osteosarc-oma specimens and divided them into three parts by Enneking staging system:11 cases of I stage,20,cases of Ⅱ stage,20 cases of Ⅲ stage.20 cases of osteochondroma as control group.We tested P-gp, PCNA andMVD of CD34 markers resectively,instead of proliferation and drug resi-stance and angiopoiesis to explore the expression of P-gp in osteosarco-ma and the relationship betweenits with PCNA,CD34 and clinical sign-ificance,by immunohistochemical staining.Methods:Case data and specimens were resected specimens of ost-eosarcoma from hebei medical university third hospital from January 2007 to January 2012 surgically,a total of 51 patients,15 cases with Lung metastasis,other 36 pateients without.There are 20 cases of femur,18 cas-es of tibia,13 cases of others in OS.Immunohistochemical staining meth-od Envision measurement of two-step is used to detect PCNA and CD34 in osteosarcoma and the expression of P-glycoprotein.Results:The positive expression of PCNA rate:the osteochondro-ma group was 10%(2/20);Osteosarcoma group was 58.9%(30/51),thereare significant difference.MVD of CD34 makers:the MVD value ofosteochondroma was 53.47±6.39;Osteosarcoma group was 18.20±4.55,P<0.05,the difference was statistically significant.P-glycoprotein:the positiveexpression rate of osteosarcoma was 45.1%(23/51),osteochondroma is(5%)1/20.Compared with control group,P-glycoprotein,PCNA and CD34 expre-ssion in osteosarcoma tissue increased significantly,the above differenceswere statistically significant(P<0.05).The expression of P-glycoprotein c-orrelate with tumor’s Enneking stage,recurrence and metastasis in patie-nts with osteosarcoma,which is statistical significance.And there is no statistical significance in gender,age,position and tumor diameter.The exp-ression of PCNA in osteosarcoma Enneking stage,pulmonary metastasis,r-ecurrence and tumor diameter was different statistically significant,and there was no statistically significantdifference in gender,age,position.The expre-ssion of MVD in osteosarcoma Enneking stage,and tumor diameter wasdifferent statistically significant,and there was no statistically signifycant difference in gender,age,position,recurrence and metastasis.Conclusions:The expression of P-glycoprotein is nonspecific in ost-eosarcoma,but it is high expression in osteosarcoma.P-gp also can be u-sed as an indictor of judging tumor nature,and evaluate the prognosis forclinicians making reasonable treatment plan to provide a basis.The expr-ession of PCNA can independent as an indictor for prognosis of patient-s with osteosarcoma,and the combination of P-glycoprotein and PCNA could make more accurate prognosis,to provide the basis for guidingclin-ical application.Almostly,there is different levels of expression of CD34 in all osteosarcoma,which is closely related to angiogenesis.CD34 protein not correlate with P-gp.MVD can be used as independent factors of pr-ognosis to guide clinical application.Drug resistance may have nothing to do with the formation of blood vessels,or need to expand samplesize to further study.So far,resistance in the process of the treatment of osteosa-rcoma is a clinical problem not solved.Deep understanding to the drugr-esistant mechanism study is very important.Only after the comprehensivetreatment of many-sided,it is likely to reverse drug resistance,and impro-ve patient surial.