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The Study Of The Immune Phenotype Of Ki-67,EMA,PR And CD34 And The Clinical Pathological Characteristics In The Meningioma

Posted on:2018-06-18Degree:MasterType:Thesis
Institution:UniversityCandidate:Houda Abdourahman IbrahimFull Text:PDF
GTID:2334330515479015Subject:Clinical pathology
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Background:Meningioma is a type of tumor that grows from the meningesmembranes that surround the brain and spinal cord.Meningioma is a heterogeneous tumor,Despite the fact that most of the meningioma is benign and slow growth of course,some cases will be aggressive behavior and to conventional treatment is invalid,Therefore,further in-depth understanding of prognostic factors and patient survival,recurrence,and the relationship between the tumor grade is necessary,such study can make us improve the accuracy of prediction for tumor biological behavior,and choose the best treatment for the patient.The prognosis of commonly used indicators include surgical removal of integrity,patient age,gender,and tumor grade.These factors have been detailed discussed in the literature.However,the relationship between the various kinds of molecular markers and prognosis also need further research.Some scholars research and discovery of new biomarkers to help clear the prognosis of patients with meningiomas.To date,several markers have been established as prognostic factors for meningioma’s.Although most meningioma’s are benign and slow growing,malignant meningioma’s are much more aggressive and refractory to traditional methods of treatment.Therefore,it is important to develop an improvedunderstanding of prognostic factors associated with survival,recurrence,and tumor grade.Such knowledge will allow for a greater accuracy in predicting tumor behavior in malignant meningioma’s and aid in selecting optimal treatment regimens.General prognostic factors such as extent of surgery,age,and tumor grade have been well documented,while the association between various molecular alterations and prognosis requires further elucidation.Counting the proliferation index(Ki-67)is the most commonly used evaluation index of meningioma cell proliferation activity.Compared with no recurrence of meningiomas,high proliferation index and is closely related to poor prognosis and recurrence of meningiomas.However,the Ki-67 index is not affirmed as a factually critical indicator of recurrence in gross-completely uprooted kind meningioma.EMA is the most specific positive marker of meningiomas because the majority of meningiomas are immune-reactive for vimentin and EMA.EMA is particularly reactive in the epithelial variants such as the microcytic and the secretory subtypes.In the recent 20 years,the relationship between sex hormone receptors and meningioma has been widely studied,the researchers found that most of the meningioma expression PR without expression of ER,and PR with the patient’s age,sex,tumor location and tumor size are not related.Other researchers reported in a high risk of recurrence of meningiomas PR expression into a downward trend.Two researchers noted the expanded presence of PRs in the meningotheliomatous type with no relation between PR status and histological subtype.CD34 is an endothelial cell marker and used as a proxy for estimating vascularity.its low level of detectability did not suggest efficacy of anti-angiogenic therapy for more than of subset of meningioma’s.Further study is warranted to evaluate the biological significance of CD34 and whether anti-angiogenic treatment may be effective in CD34 positive tumors.CD34 reactivity has been shown to be present in approximately 15%of meningioma’s.Objective:To analyze the immune phenotype of Ki-67,EMA,PR and CD34 in the meningioma and to to explore the relationship between the clinical pathological characteristics and prognosis.Materials and methods:we obtained a written informed consent from 127 enrolled patients with Meningioma from October 2015 to March 2016.The 127 patients were 38 males and 89 females,80 patients were>50 years,and 47 were<50 years old.All study participants underwent clinical examinations to ascertain the presence of meningioma.At least two experienced oncologists performed the diagnosis of meningioma.Diagnosis was confirmed by magnetic resonance imaging(MRI),Pathological,histological and immune-histochemical investigations were all part of the examination.Information collected during examination included patient’s name,gender,age,location of meningioma,grade of the meningioma,clinical score,and the presence or absence brain invasion.Patients were followed up for the entire period of the study or loss to follow-up or death.Follow-ups include re-examination of patients and monitoring of the meningioma’s.All initial and follow-up data were recorded for further analyses.All the specimens fixed 6-48 hby 10%formaldehyde,and performed HE and immunochemical stain(The antibody was provided by the Beijing Zhongshan biological co.,LTD).Positive result judgment:By double-blind method put forward by the reference Fromowitz dyeing standard to evaluate tinting strength was divided into Colorless(-)to 0 points,light yellow(+)for 1 minute,yellow(+ +)for 2 minutes,tan(+ + +)for the three points.Positive cells number percentage as follows:30%to 0 or less points,31%to 70%to 1,and 71%for 3 or more points.The score obtained two scores assessed the result:0 was divided into negative,(1-2)was divided into weak positive(+),(3-4)was divided into moderate positive(++),(5-6)was divided into strong positive(+ + +).Statistical Analysis:We used Student’s t test to compare continuous variables,and Chi-square test to compare categorical variables.We also used univariate and multivariate Cox regression analyses to investigate the factors associated with meningioma.We used the chi-square test to compare EMA expression and the relationship between different clinical characteristics and pathological subtypes.We performed all statistical analyses using SPSS 18.0 software.A two-sided test with P<0.05 was considered statistically significant except otherwise specified.Results:(1)General data.Investigation of the location of the meningioma revealed that 74(58.3%)were located on the convexity of the brain,16(12.6%)cranial fossa,2(1.6%)tentorial,11(8.7%)parasagittal and parafalcine,and 24(18.9%)else.We classified the patients according to the 2007 WHO criteria and found that 89 cases(70.1%)were Grade I and 33 cases(26.0%)were Grade II.The study included a total of 127 patients,consisting of 38(29.9%)males and 89(70.1%)females.Out of the 127 patients,80(63.0%)were>50 years and 47(37.0%)were<50 years old.We divided our study participants into two groups based on tumor size(<5 cm3 and>5 cm3).Our study revealed that 92(72.4%)of study participants had tumor size<5 cm3,and 35(27.6%)of participants had tumor size>5 cm3.Classification of patients by Simpson’s grade revealed that 44(34.6%)of patients were Grade I and 83(65.4%)were Grades Ⅱ-Ⅴ.Out of the 127 patients,14(11.0%)had brain invasion of the meningioma and 113(89.0%)had no invasion of the brain.Our analysis of study participants by the presence of perifocal edema revealed that 19(15.0%)of cases had perifocal edema,while 108(85.0%)cases had no perifocal edema.Investigation of the presence of tumor recurrence revealed that 9.4%of cases had tumor recurrence and 90.6%had no tumor recurrence Nine(7.1%)of our study subjects withdrew from the study,10(7.9%)subjects died during the study period,and 108(85.0%)were alive at the end of the study(Fig 4.6).Overall,117(92.1%)of participants were censored during the study.Out of the 127 study subjects,114(89.8%)were EMA(Epithelial Membrane Antigen)positive and 13(10.2%)were EMA negative;while 36(28.3%)were CD34 positive and 91(71.7%)were CD34 negative.We summarize the expression of KI-67 and Progesterone Receptor(PR)by the meningioma’s.Ninety-eight cases(77.2%)expressed<4%KI-67,19(15.0%)expressed 4-19%KI-67,and 10(7.9%)cases expressed ≥ 20%KI-67.Out of the total 127 study subjects 50(39.4%)expressed≤10%PR,44(34.6%)expressed 11-50%PR,and 33(26.0%)expressed>50%(2)Differences characteristics based on WHO grades.Based on WHO grades,we found significant differences by gender,tumor recurrence,brain invasion,EMA and Ki-67 expression(All P<0.05).WHO Grade I meningioma tumors had a higher incidence among females(82.02%)than among males(17.98%).While WHO Grade Ⅱ meningioma tumors had a higher incidence among males(57.89%)than among females(42.10%).WHO Grade Ⅱ(21.05%)meningioma tumors had more recurrence rates than Grade I(4.49%)meningioma.Grade Ⅱ(31.58%)meningioma had more Brain Invasion than Grade I(2.25%)meningioma.While Grade I(94.38%)meningioma had more EMA positive rate than Grade Ⅱ(78.94%)Meningioma.Grade I(96.62%)meningioma had more<4%Ki-67 expression rates than Grade Ⅱ(31.58%).While WHO Grade Ⅱ(44.74%and 23.68%)meningioma tumors had more of 4-19%and>20%Ki-67 expressions than Grade Ⅰ(2.24%and 1.12%)meningioma.Correlation analyses revealed a significant negative correlation between EMA and Ki67(r=-0.340,P<0.05).(3)Differences characteristics based on the presenceof tumor brain invasionWe found significant differences by Simpson’s Grade,WHO Grade,(All P<0.05).we found significant differences in Simpson’s Grade I(64.28%)more than Simpson’s Grade Ⅱ-Ⅳ(31.25%)(P<0.05).WHO Grade Ⅱ(33.33%)meningioma tumors had more Brain Invasion than Grade I(2.24%)meningioma.P<0.01(4)Differences characteristics based on the subjects with and without recurrent meningioma.we found significant differences between subjects with and without recurrent meningioma by gender,WHO grading,Ki67 expression,(All P<0.05).Tumors recurrent had a higher incidence among females(21.05%)than among males(4.49%).P<0.05.WHO Grade Ⅱ(18.18%)meningioma tumors had more recurrent than Grade 1(4.49%)meningioma.P<0.05.Recurrentrate of Ki-67<4%group(5.10%),Ki-67 4-19%group(10.52%)and>20%groups 50.00%,respectively,there are significant differences,P<0.001Conclusion:(1)meningioma incidence is given priority to the women and age>50 years.,more women than men in WHO Grade Ⅰ,and less women than men in Grade Ⅱ.We also found female had more recurrence rates than males.(2)WHO Grade Ⅱ meningioma tumors had more recurrence rates and brain Invasion than Grade Ⅰ meningioma.(3)While Grade Ⅰ meningioma had more EMA positive rate than Grade Ⅱ Meningioma.Grade Ⅰ meningioma had more<4%Ki-67 expression rates than Grade Ⅱ While WHO Grade Ⅱ meningioma tumors had more of 4-19%and ≥20%Ki-67 expressions than Grade I meningioma.Correlation analyses revealed a significant negative correlation between EMA and Ki67.Rrecurrentrate of Ki-67<4%group is lowest,Ki-67 4-19%group is higher,and≥20%groups is highest.(4)In case of the presenceof tumor brain invasion,We found Simpson’s Grade I have been more adopted than Simpson’s Grade Ⅱ-Ⅳ.
Keywords/Search Tags:meningioma, immuno-phenotype, prognosis, WHO grade
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