The Expression And Clinicopathologic Significance Of CD133,CD44~+/CD24~-,CD44~-/CD24~+ In Different Stages Of Breast Carcinogenesis

[Objective]To study the expression and clinicopathologic significance of CD133,CD44~+/CD24~-,CD44~-/CD24~+ in different stages of breast carcinogenesis(benign breast hyperplasia,breast atypical hyperplasia,breast carcinoma in situ,invasive breast cancer),and their relationship with clinical-pathologic parameters in breast carcinomas,and to explore the correlation between CD133 and CD44~+/CD24~-,CD44~-/CD24~+.[Methods]We investigated the paraffin-embedded tissues of 121 cases of breast carcinomas,51 cases of breast carcinoma in situ,39 cases of atypical hyperplasia breast tissues,41 cases of benign hyperplasia breast tissues and 45 cases of normal breast tissues.Double-staining immumohistochemical(IHC) was applied for the detection of CD44~+/CD24~-,CD44~-/CD24~+ cells and single-staining IHC for CD133. Results were compared with clinical-pathologic parameters,respectively,and the correlation between CD133 and CD44~+/CD24~-,CD44~-/CD24~+ was analyzed.[Results]1,The staining of CD133 localized mainly in cytoplasm.In normal breast tissue,there wasn't the CD133 expression.The rate of positive CD133 expression in breast cancer was significantly higher than that in breast carcinoma in situ,benign breast hyperplasia,breast atypical hyperplasia(P＜0.01),and the rate of positive CD133 expression was 74.4%(90/121),64.8%(33/51),48.7%(19/39),31.7%(13/41) respectively.2,The positive expression rate of CD133 was 63.6%(21/33),72.7%(26/36),82.7%(43/52) in gradeⅠ,gradeⅡ,and gradeⅢ,respectively(P＜0.05).The positive expressin rate of CD133 was 94.3%(33/35) in stageⅣinvasive breast cancers,which was significantly higher than that in stageⅠ,57.1%(12/21);stageⅡ,69.4%(34/49); stageⅢ,68.7%(11/16).There is statistically significant difference(P=0.000).The positive expression rate of CD133 was 82.0%(41/50),69.0%(49/71) in breast carcinomas with axillary lymph node matestasis and without axillary lymph node metastasis respectively(P＜0.05).The positive expression rate of CD133 in breast invasive carcinomas with blood matestasis was higher than that in matestasis-free breast invasive carcinomas,the former was 94.3%(33/35),the latter was 66.3%(57/83) (P＜0.05).The expression of CD133 was significantly higher in breast cancers with recurrence than that in breast cancers without recurrence(82.8%vs 64.9%)(P＜0.05). Kaplan-Meier analysis demonstrated that a positive expression of CD133 was associated with poor overall survival and relapse-free survival(both P＜0.05). However,CD133 expression was not correlative with the age of patients,menopausal status,histological type,tumor size,ER,PR,Her-2(P＞0.05).Moreover,Cox regression model confirmed the expression of CD133 as an independent prognositic factor(P＞0.05).3,The staining of CD44~-/CD24~+ localized in membrance in most of cases,and in cytoplasm in part of invasive carcinomas.In normal breast tissue,CD44~-/CD24~+ was rarely expressed.Only focally an apically accentuated membranous staining of ductal epithelium.Dilated ducts virtually always displayed a strong apical immunoreactivity. The expression of CD44~-/CD24~+ in normal breast tissue is 33.3%(15/45),which of 96.6%positive cases were less than 10%positive percentage.The rate of positive CD44~-/CD24~+ expression was respectively 43.9%(18/41),53.8%(21/39), 68.6%(35/51),86%(104/121) in benign breast hyperplasia,breast atypical hyperplasia, in breast carcinoma in situ,invasive breast cancer(P＜0.001).4,The positive expression rate of CD44~-/CD24~+ was 78.8%(25/33),88.9%(32/36),88.5%(48/52) in gradeⅠ,gradeⅡ,and gradeⅢ,there is significantly statistical meaning(P=0.006).The positive expressin rate of CD44~-/CD24~+ in stageⅠ,stageⅡ, stageⅢ,stageⅣwas 76.2%(16/21),85.7%(41/49),87.5%(14/16),91.4%(32/35), respectively(P＜0.01).The expression of CD44~-/CD24~+ in invasive breast cancers with matestasis was higher than that in patients without matestasis(91.4%,32/35 vs 83.7%,72/86)(P=0.000).The positive expressin rate of CD44~-/CD24~+ was 90.6%(58/64),80.7%(46/57) in breast cancers with recurrence and without recurrence(P＜0.05).However,CD44~-/CD24~+ expression was not correlative with the age of patients,menopausal status,histological type,lymph node matestasis,tumor size,ER,PR,Her-2(P＞0.05).Kaplan-Meier analysis demonstrated that a positive expression of CD44~-/CD24~+ wasn't associated with overall survival and relapse-free survival(both P＞0.05).Moreover,Cox regression model confirmed the expression of CD44~-/CD24~+ as an independent prognositic factor(P＞0.05).5,The staining of CD44~+/CD24~- localized mainly in cell membrace.In normal breast tissue,the prevalence is 20%(9/45).The rate of positive CD44~-/CD24~+ expression was 29.3%(12/41),35.9%(14/39),43.1%(22/51),52.9%(64/121) respectively(P＜0.05).6,CD44+/CD24- expression in invasive breast cancer with lymph node matestasis was higher than that in invasive breast cancer without lymph node matetasis(64%32/50 vs 43.7%31/71)(P＜0.05).Its expression was not associated with the age of patients, menopausal status,histological type,histiological grade,TNM stage,matestasis, tumor size,overall survival,replase-free survival,ER,PR,Her-2(P＞0.05).Cox regression model confirmed the expression of CD44-/CD24+ as an independent prognositic factor(P＞0.05).7,CD133 and CD44-/CD24+ weren't positive correlation in benign breast hypertasis and atypical breast hypertasis(P＞0.05).The positive correlation between CD133 and CD44-/CD24+ was found in carcinomas in situ and invasive breast cancer(γ=0.408, P=0.003).In 67%invasive breast cancer(87/121) expessed both CD133 and CD44-/CD24+.The higher the positive percentage of CD44-/CD24+ was,the more the positive expression of CD133 was(γ=0.217,P=0.017).There weren't the correlation between CD133 and CD44+/CD24- in different stage of breast carcinogenesis.[Conclusions]1.There is no expression of CD133 in normal breast tissues.The CD44~-/CD24~+, CD44~+/CD24~- have rarely expression in normal breast tissues.2.There is significant statistical difference that CD133,CD44-/CD24+, CD44+/CD24-were expressed in breast cancer,breast carcinoma in situ,atypical hyperplasia breast tissue,uaual hyperplasia breast tissues and normal mammary gland tissue.3.The strongly positive expression rate of CD133 in breast invasive ductal carcinoma group was correct to histologieal grading,TNM staging,nodal status,matestasis, recurrence,event-free survival,overall survival.CD133 couldn't make as an indepentant prognosis factor.There was no significant correlation between CD133 tumor cell prevalence and age,histological type,tumor size,menopausal status, estrogen receptor,progesterone receptor,HER-2.4.The positive expression rate of CD44~-/CD24~+ in breast invasive ductal carcinoma group was correct to histologieal grading,TNM staging.nodal status,recurrence. CD44~-/CD24~+ couldn't make as an indepentant prognosis factor.There was not significant correlation between CD44~-/CD24~+ tumor cell prevalence and age. histological type,tumor size,menopausal status,event-free survival,overall survival. estrogen receptor,progesterone receptor,HER-2.5.The CD44~+/CD24~- expression in invasive breast was correlation nodal status.There was not signifincant statistics meaning between CD44~+/CD24~- and age,menopausal status,histological type,tumor size,histologieal grading.TNM staging.metatisis. recurrence,event-free survival.overall survival,estrogen receptor,progesterone receptor,HER-2.6.The correlation between CD133 and CD44~-/CD24~+ in carcinomas in situ and invasive breast cancer was found.Investigating expression conditions may help to understand and evaluate the malignant condition of breast carcinoma and the prognosis of the patients in multiple respects.