A Meta-analysis Of Expressions Of Bcl-2, Ki-67, P16, P53Arid ER In Uterine Leiomyosarcoma And Their Clinical Applications

Objective: We investigated the expressions of bcl-2, Ki-67, p16, p53and ER in uterine leiomyosarcoma (uLMS) and their clinical values.Methods: Based on the principles of evidence-based medicine, we madea META analysis of uterine leiomyosarcoma by searching for medicalliterature about pathological diagnostic sensitivity of uterineleiomyosarcoma in MEDLINE(1966-2014), CNKI(1994-2014), VIP(1989-2014)and Wang fang(1990-2014)． We used uLMS, leiomyosarcoma of uterus,uterine leiomyosarcoma as key words． We selected the literatures on thebasis of including and excluding standards in advance. All theimmunohistochemical results extracted had been put in RevMan5.0and Stata12.0soft wares and analyzed. We used OR as dichotomous variable. Theresults of heterogeneity test-P value showed in the forest plots of Revmansoftware was used to judge the heterogeneity of the research. The researchwhich was with homogeneity was calculated by solid-effect model while theheterogeneity was calculated by random-effect model. We used Z value orP value showed in the forest plots to judge whether the conclusions hadstatistical significance. The publication bias were analyzed by thedegree of symmetry manifested in the funnel plots from Revman softwareand Egger’s method from Stata software. The sensitivity analysis wasperformed in two models above at the same time.Results: According to the including and excluding standards,27papers were finally selected,12in foreign language and15in Chinese.The analysis of expression of p16in uLMS patients manifested that:①uLMS versus non-uLMS：the expression of p16in uLMS patients had nohomogeneity（P＜0.00001）, but had statistical significance between uLMSand non-uLMS（Z=4.70, P＜0.00001）.②uLMS versus other types of USMT：the expression of p16in uLMS patients shared the homogeneity（P=0.40＞0.1）, and had statistical significance between uLMS and other typesof USMT（Z=10.88, P＜0.00001）. The analysis of expression of p53inuLMS patients manifested that:①uLMS versus non-uLMS： the expression of p53in uLMS patients had no homogeneity（P=0.0009＜0.1）, but hadstatistical significance between uLMS and non-uLMS（Z=10.73, P＜0.00001）.②uLMS versus other types of USMT： the expression of p53inuLMS patients shared the homogeneity（P=0.16＞0.1）, and had statisticalsignificance between uLMS and other types of USMT（Z=10.76, P＜0.00001）.The analysis of expression of Ki-67in uLMS patients manifested that:①uLMS versus non-uLMS：the expression of Ki-67in uLMS patients had nohomogeneity（P＜0.0001）, but had statistical significance between uLMSand non-uLMS（Z=2.25,P=0.02＜0.05）.②uLMS versus other types of USMT：the expression of Ki-67in uLMS patients shared the homogeneity（P=0.69＞0.1）, and had statistical significance between uLMS and other typesof USMT（Z=6.24, P＜0.00001）. The analysis of expression of bcl-2inuLMS patients manifested that: the expression of bcl-2in uLMS patientshad no homogeneity（P=0.002＜0.1）, but had statistical significancebetween uLMS and other types of USMT（Z=3.51, P=0.0005）. The analysisof expression of ER in uLMS patients manifested that:①uLMS versusnon-uLMS：the expression of ER in uLMS patients had no homogeneity（P=0.05＜0.1）, but had statistical significance between uLMS and non-uLMS（Z=3.81, P=0.0001）.②uLMS versus other types of USMT：the expressionof ER in uLMS patients shared the homogeneity（P=0.28＞0.1）, and hadstatistical significance between uLMS and other types of USMT（Z=5.48,P＜0.00001）.③uLMS versus other types of US： the expression of ER inuLMS patients shared the homogeneity（P=0.31＞0.1）, and had statisticalsignificance between uLMS and other types of US（Z=2.14, P=0.03＜0.05）.The publication bias analysis showed that the positive expressions of p16,p53and ER in uLMS patients were slight asymmetry in funnel plots and inEgger’s test, P value＜0.05, which suggested that there existedpublication bias. While other index showed no publication bias. Theresults of sensitivity analysis suggested that all the results were stableand had no significant differences.Conclusion： This research found out that uLMS patients have veryspecial pathological features：①Most of the patients had high expressionof p16. Among uLMS patients and other types of USMT patients, the positiveexpression of p16had statistical significance which we can use it to distinguish uLMS patients from other types of USMT patients. But we stillcan’t use p16to differentiate uLMS patients from other types of USpatients； Although diffuse and strong-positive expression of p16mayindicate a good prognosis for uLMS patients, there still needs morelarge-sample studies to confirm it.②Most patients had high expressionof p53. Among uLMS patients and other types of USMT patients, the positiveexpression of p53had statistical significance which we can use it todistinguish uLMS patients from other types of USMT patients. But we can’tuse p53to differentiate uLMS patients from other types of US patientsuntil now； Some authors agreed that p53seemed to be related to stageand most studies pointed out that low expression of p53indicated a betterprognosis. But we can’t use p53as an independent prognosis factor.③Most patients had high expression of Ki-67. Among uLMS patients and othertypes of USMT patients, the positive expression of Ki-67had statisticalsignificance which we can use it to distinguish uLMS patients from othertypes of USMT patients. But we still can’t use Ki-67to differentiate uLMSpatients from other types of US patients； Some studies found out thatpositive expression of Ki-67may shorten patients’ survival time anddisease-free survival.④The majority of patients had middle-lowexpression of ER. Among uLMS patients and other types of USMT patients,the positive expression of ER had statistical significance which we canuse it to distinguish uLMS patients from other types of USMT patients.So as with uLMS patients and other types of US patients. Since we didn’tuse large-sample studies, there still needs further research to confirmit； Some studies indicated that patients with middle-low expression ofER may have the best prognosis. And someone found out that it can lengthensurvival time and improve life standard that patients used letrozole inclinical trials. When we use more letrozole for treatment in the future,we may obtain more definite conclusions of curative effect.⑤Mostpatients had low expression of bcl-2. Among uLMS patients and other typesof USMT patients, the positive expression of bcl-2had statisticalsignificance which we can use it to distinguish uLMS patients from othertypes of USMT patients；Authors of some studies concluded that bcl-2couldbe used as an independent prognostic factor and some literates agreed that bcl-2could improve prognosis and delay recrudescent time as well. In oneword, the majority of uLMS patients have high expression of p16, p53andKi-67, low-middle expression of ER and low expression of bcl-2. Combinedwith the unique pathological features of uLMS patients and referenceliteratures, it suggested that the better prognosis may be related tooverexpression of bcl-2, moderate expression of ER and low expression ofp16, p53and Ki-67. As the literatures included in this study are allcase-control studies whose argument strength is low, and there existscertain publication bias in some of the analysis results, so we need tostudy more high-quality case-control tests and large sample prospectivestudies as well to make the perfect choices on the diagnosis and prognosisfor uLMS patients.