儿童侵袭性成熟B细胞淋巴瘤的临床病理学及分子遗传学特点

目的 分析总结中国儿童各类型侵袭性成熟B细胞淋巴瘤的临床病理学及分子遗传学特点,为其诊断的标准化提供依据.方法 收集97例儿童侵袭性成熟B细胞淋巴瘤石蜡包埋组织标本,包括伯基特淋巴瘤(BL)81例、弥漫大B细胞淋巴瘤(DLBCL)8例、介于BL和DLBCL间的不能分类的B细胞淋巴瘤(BL/DLBCL)8例,利用免疫组织化学技术和间期荧光原位杂交(FISH)技术检测其免疫表型和分子遗传学特征.结果 BL的bcl-2和MUM1的阳性率分别为3%(2/66)和17%(12/71),DLBCL分别为50%(4/8)和63%(5/8),BL/DLBCL分别为50%(4/8)和63%(5/8).BL、DLBCL和BL/DLBCL的Ki-67平均值分别为(93±4.4)%、(83±14.3)%和(80±11.5)%.BL、DLBCL和BL/DLBCL的c-myc基因易位的比例分别为98%(79/81)、38%(3/8)和50%(4/8).38%(3/8)的DLBCL和25%(2/8)的BL/DLBCL存在bcl-6基因的多拷贝,BL与DLBCL之间、BL与BL/DLBCL之间bcl-2、MUM1和Ki-67平均值的差异及c-myc基因易位和bcl-6基因多拷贝的差异均有统计学意义(均P＜0.05).结论 儿童侵袭性成熟B细胞淋巴瘤的诊断和分型需要综合分析形态学、免疫表型和分子遗传学特征.儿童BL/DLBCL可能是DLBCL的一个亚型.CD10+、bcl-6+、bcl-2-、Ki-67＞90%、伴有IGH/c-myc重排、不伴有bcl-2和bcl-6重排时,支持BL的诊断;bcl-2+、Ki-67为50%～90%,同时伴有bcl-6基因的多拷贝时,支持DLBCL或BL/DLBCL的诊断.     

bcl-2与乳腺癌耐药蛋白基因在弥漫大B细胞淋巴瘤中表达的意义

目的 研究bcl-2和乳腺癌耐药蛋白(BCRP)基因在非霍奇金淋巴瘤(NHL)中的表达及其相关性.方法 对初治弥漫大B细胞淋巴瘤(DLBCL)患者(40例)淋巴结组织液,采用流式细胞术(FCM)及反转录聚合酶链反应(RT-PCR)技术定量检测其BCRP mRNA的表达,同时将患者标本常规石蜡包埋、HE染色和链霉菌素牛物素技术(LSAB)免疫组织化学法标记bcl-2蛋白表达.结果 40例DLBLC患者的bcl-2与BCRP的阳性表达率分别为60.0%(24/40),37.5%(15/40),不同临床分期的DLBCL患者,BCRP阳性表达率差异有统计学意义(x2=6.0606,P<0.05).bcl-2、BCRP表达阳性组有效率低于表达阴性组,差异有统计学意义(x2=5.7618,P<0.05;x2=6.5541,P<0.05);bcl-2和BCRP表达均阳性与均阴性患者的疗效比较,差异无统计学意义(x2=2.0263,P>0.05).结论 BCRP可能在DLBCL的原发多药耐药中发挥重要作用,并有助于化疗疗效的评估及提示疾病转归;bcl-2在DLBCL中的表达对肿瘤恶性程度及预后的判断均有一定意义;联合检测bcl-2和BCRP基因对评价DLBCL预后有较大意义.     

P53突变蛋白表达对弥漫大B细胞淋巴瘤预后的预测作用

目的 探讨p53突变蛋白表达对弥漫大B细胞淋巴瘤(DLBCL)预后的预测作用,指导个体化治疗.方法 随机选择初治DLBCL患者62例,应用免疫组织化学方法检测p53突变蛋白和CD10、bcl_6、MUM1的表达,分析p53突变蛋白表达与患者临床特征、分子分型以及预后的关系.结果 48.4%(30/62)的患者表达p53突变蛋白.p53突变蛋白表达与初始治疗反应有关(x2=20.365,P=0.040),阳性组的完全缓解率为33.3%(10/30),阴性组为59.4%(19/21);与分子分型有关(x2=31.023,P=0.021),阳性组非生发中心型比例显著高于阴性组,分别为83.3%和56.2%;与其他临床特征无关.多因素生存分析显示p53突变蛋白表达是独立的预后预测因子,阳性组的无进展生存期和中位生存期均短于阴性组(x2=36.784,P=0.005和x2=35.276,P=0.006).结论 p53突变蛋白表达是DLBCL独立的不良预后因子,能够用来指导个体化治疗.     

CD20在成年人急性B淋巴细胞白血病中的表达及其临床意义

目的 检测CD20在成年人急性B淋巴细胞白血病(B-ALL)的表达,探讨其与临床特点的相关性.方法 回顾性总结分析96例成年B-ALL患者CD20表达情况,结合其临床特性和治疗转归进行分析.结果 96例成年B-ALL患者中,CD20阳性29例(30.20%),CD20阴性67例(69.79%).CD20阳性组与阴性组男女比分别为1.42∶1和1.79∶1(x2=0.27,P＞0.05),中位年龄分别为28岁与23岁,肝脾及淋巴结浸润比例分别为44.83%和41.38%、40.30%和35.82%,髓系抗原表达比例分别为51.72%与56.72%,Ph染色体和bcr-abl融合基因阳性比例分别为24.14%与28.36%,4周内完全缓解率分别为73.08%与68.85%,差异均无统计学意义(P值均＞0.05).在复发率和3年总体生存率上,CD20阳性组分别为54.55%与14.80%,CD20阴性组分别为29.63%与37.30%,两组间差异有统计学意义(x2=0.42,x2=5.31;P值均＜0.05).结论 CD20在成年人B-ALL表达与临床特点无相关性,但对判断患者的预后有一定的指导意义.     

原发性扁桃体滤泡性淋巴瘤的临床病理特征

目的:按照WHO 2008年淋巴造血组织肿瘤的最新分类,对原发性扁桃体滤泡性淋巴瘤(FL)的临床特征、形态学和免疫表型进行观察分析,探讨其与淋巴结原发性FL的异同,以利于诊断和鉴别诊断.方法:复习37例原发于扁桃体FL患者的临床资料及诊断切片,免疫组织化学染色后观察LCA、CD20、CD79a、CD45RO、CD3、CD10、Bcl-6和Bcl-2的表达情况.结果:37例原发性扁桃体FL患者中,活检前临床诊断扁桃体肿物28例,扁桃体癌6例,淋巴瘤3例.组织形态与淋巴结内FL类似,滤泡型4例,滤泡和弥漫型1例,少滤泡型32例,无弥漫型.低级别(1-2级)17例,高级别(3级)20例.免疫组织化学染色均表达LCA及B细胞标记物CD20和CD79a,不表达CK及T细胞的标记物CD45RO和CD3.CD10阳性率43.24%,Bcl-6阳性率86.48%,CD10和Bcl-6共表达率为37.83%;22例表达Bcl-2,阳性率59.46%;CD10、Bcl-6、Bcl-2在低级别FL和高级别FL中的表达率比较差异均无统计学意义(P>0.05).2例发生在儿童的扁桃体FL其形态及免疫表型均与WHO新分类的儿童FL相同.结论:扁桃体FL组织形态与淋巴结FL相似,本组活检标本中以少滤泡型为主,高级别占多数.B细胞和生发中心标记物的表达情况与淋巴结FL基本一致,而Bcl-2表达低.     

成年人伴CD2表达B系急性淋巴细胞白血病免疫表型特征分析

目的 了解成年人伴CD2表达B系急性淋巴细胞白血病(CD+2 B-ALL)的免疫表型特征,为临床诊断、治疗及预后判断提供依据.方法 应用流式细胞术及多种单克降抗体检测18例成年人CD+2B-ALL及68例CD-2 B-ALL患者的免疫表型,并对其结果进行分析比较.结果 CD+2 B-ALL的发病年龄明显小于CD-2 B-ALL,18例成年人CD+2 B-ALL的大部分表面标志物与CD-2 B-ALL相似,其中CD10表达水平[(73.78±26.67)%]高于CD-2 B-ALL[(52.84±35.25)%],差异有统计学意义(t=2.35,P<0.05),CD33表达水平[(15.46±27.41)%]则低于CD-2 B-ALL[(31.15±27.72)%],差异有统计学意义(t=2.16,P<0.05);所有B-ALL患者都高表达CD34,阳性表达率分别为72.2%(13/18)和80.9%(55/68),差异无统计学意义(χ2=0.64,P>0.05).CD+2 B-ALL的CD20阳性率明显低于CD-2 B-ALL,差异有统计学意义(χ2=11.38,P<0.05).CD+2 B-ALL伴髓系抗原(CD13或CD33)表达率为44.4%(8/18),明显低于CD-2 B-ALL的72.1%(49/68),差异有统计学意义(χ2=4.86,P<0.05).结论 成年人CD+2 B-ALL与CD-2 B-ALL具有相似的免疫表型,主要来源于造血干细胞的恶性转化,CD+2 B-ALL伴髓系抗原(CD13、CD33)及CD20表达明显低于CD2 B-ALL,提示成年人CD+2 B-ALL可能有较好的预后.     

原发系统性间变性大细胞淋巴瘤临床病理特征及免疫表型分析

目的 分析原发系统性间变性大细胞淋巴瘤( ALCL)的临床病理特征和免疫组织化学特点,提高诊治水平。方法选取22例ALCL患者,均进行分期、国际预后指数(IPI)、乳酸脱氢酶(LDH)检测,应用免疫组织化学SP法检测间变性淋巴瘤激酶(ALK)、Ki-67、Caspase-3、CD30、EMA、Granzyme B等,回顾性分析患者临床、病理形态学资料、免疫表型及生物学特性,并进行预后分析。结果22例均为原发系统性ALCL,ALK+ 15例(68.2％),ALK-7例(31.8％);AILK+患者发病年龄、Ki-67增殖指数较ALK-患者低,Caspase-3表达率高,差异有统计学意义(x2 =4.618,P= 0.032);15例ALK+ALCL均表达CD30和EMA。ALCL中ALK的表达与Ki-67、Caspase-3的表达呈负相关(r= -0.581,P= 0.006;r=0.458,P=0.032)。ALK+病例较ALK-病例GranzymeB(x2=0.11,P=0.74)、TIA-1( x2= 0.01,P=0.92)的表达率高,但差异无统计学意义(P＞0.05)。有效率为54.5％(12/22),其中完全缓解率为18.2％(4/22);全组中位生存期12个月,1年生存率为59.1％( 13/22),2年生存率为50.0％(11/22)。Ann Arbor分期、LDH及IPI与疾病预后相关。结论ALK+较ALK-ALCL患者核增殖低,恶性程度低,临床特征和免疫表型具有一定的特征性;ALK、Ki-67、Caspase-3、分期、血清LDH及IPI对预测ALCL患者的生存和指导治疗有帮助。     

中国人经典霍奇金淋巴瘤中人类白细胞共同抗原表达的研究

目的 既往的研究发现在高加索人中,经典霍奇金淋巴瘤肿瘤细胞人类白细胞共同抗原(HLA)的表达与EB病毒感染密切相关,研究在亚洲人中两者的相关性.方法 随机选取北京大学医学部病理学系常规外检及会诊病例中确诊为经典霍奇金淋巴瘤的145例,所有病例均有石蜡包埋组织蜡块.常规HE染色、形态学观察,根据WHO分类标准对所有病例进行重新分类.原位杂交方法检测EB病毒编码的小RNA(EBER)以提示肿瘤与EB病毒的相关性.HLA-Ⅰ类抗原的表达使用HC-10和β 2-微球蛋白抗体检测,而HLA-Ⅱ类抗原的表达使用CR3/43抗体检测.结果 145例中,40%(58例)的病例为EB病毒相关性.EB病毒阳性病例中,混合细胞型较结节硬化型更为常见(71%比16%,P＜0.001).HLA-Ⅰ类抗原在EB病毒阳性病例中的表达率明显高于EB病毒阴性的病例(79%比30%,P＜0.001).而HLA-Ⅱ类抗原的阳性率在EB病毒阳性和阴性病例中差异无统计学意义(52%比43%,P=0.277).结论 中国人经典霍奇金淋巴瘤HLA-Ⅰ类抗原的表达与EB病毒感染密切相关,与高加索人一样,但HLA-Ⅱ类抗原的表达与EB病毒感染无显著相关性.     

艾滋病病毒感染合并口腔浆母细胞型淋巴瘤一例临床病理分析

目的 分析艾滋病病毒(HIV)合并口腔浆母细胞型淋巴瘤的形态学特点、免疫表型及鉴别诊断.方法 对1例HIV合并口腔浆母细胞型淋巴瘤进行形态学、免疫组织化学分析及文献复习.结果 免疫组织化学显示CD-20、CD-3、CD-45、CD-30、ALK(-)、EBV(+)、CD138灶(+)、Ki-67 90%(+)、EMA灶(+)、CD68组织细胞(+)、CDRB灶(+)、CD45RO个别(+)、CD-79a、CD-56、IgM、IgG、IgA、HMB45、bcl-2、CD5、cyclinD1、CD43、CD10、Desmin、MPO、CD15、MYOD1、CK均为(-).病理诊断弥漫大B细胞淋巴瘤浆母细胞型分化.结论 弥漫性大B细胞淋巴瘤病理类型多样,HIV合并口腔浆母细胞型较少见,掌握其形态学特征,熟悉各类型的免疫表型的异同点对诊断与鉴别诊断有重要意义.     

Choi和Hans分型在弥漫大B细胞淋巴瘤预后评价中的意义

目的 探讨Choi和Hans分型在弥漫大B细胞淋巴瘤(DLBCL)预后评价中的意义.方法 收集山西省肿瘤医院病理科有详细随访资料的DLBCL 99例,用免疫组织化学EnVision法检测bcl-2、bel-6、CD10、FOXP1、GCET1、MUM-1的表达情况.根据Choi和Hans两种分类法分别将所有病例分型.其中35例应用荧光原位杂交技术检测bcl-6基因重排情况.结果 按Hans分类法生发中心B细胞(GCB)型21例,非GCB(nonGCB)型78例;按Choi分类法GCB型23例,nonGCB型76例.GCB型生存率明显优于nonGCB型,差异有统计学意义(P=0.000).FOXP1蛋白阳性表达与预后呈负相关(P=0.011),GCET1阳性表达则与预后呈正相关(P=0.027).在35例DLBCL患者中.bcl-6基因重排阳性高发于nonGCB型患者,bcl-6基因重排与bcl-6蛋白的表达没有明显相关性.结论 Choi和Hans两种分类法免疫分型GCB型预后都优于nonGCB型.bcl-6、FOXP1、GCET1的表达与预后有相关性.Choi及Hans分类法对DLBCL的免疫分型、临床预后估计均有应用价值.     

The prevalence of bcl-2, p53, and Ki-67 immunoreactivity in transitional cell bladder carcinomas and their clinicopathologic correlates

The aim of this study was to investigate the expression of bcl-2, p53 oncoproteins, and Ki-67 antigen in a series of transitional cell bladder carcinomas and its relation to the traditional prognostic indicators and patient's survival. One hundred six cases with transitional cell carcinoma (TCC) were examined for detection of bcl-2, p53 proteins, and Ki-67 antigen (MIB1 antibody). Bcl-2 immunohistochemical positivity was observed in 52% of TCCs and in 57% of low-grade and 44% of high-grade TCCs. Bcl-2 was also detected in normal urothelium and dysplastic lesions with basal cell expression, and negative staining was observed in carcinomas in situ. Tumor stage showed a significant inverse correlation with overall bcl-2 positivity. The loss of bcl-2 protein expression in higher-stage TCCs was statistically significant (Pt = .01). p53 protein was overexpressed in 50% of TCCs and more frequently in invasive and in carcinomas in situ than in superficial TCCs (Pt = .03). In contrast, detection of p53 was not observed in normal and dysplastic urothelium. p53 positivity was related to the degree of differentiation and to the stage of the disease (Pf = .01 and Pt = .03, respectively). Concerning Ki-67 antigen, its expression was found in 57.5% of TCCs. There was a strong overall correlation of Ki-67 with tumor stage (Pt = .002) and grade (Pf = .002). Univariate statistical analysis showed that the expression of p53 and Ki-67 was significantly correlated to poor prognosis (P = .02, P = .02, respectively). On multivariate analysis, none of these markers but only stage and grade were significantly correlated to prognosis (P = .02, P = .02, respectively). These findings suggest that overexpression of bcl-2 protein may be an early event in tumorigenesis. Tumors with loss of bcl-2 positivity and overexpression of p53 and Ki-67 had an unfavorable prognosis; however, in multivariate analysis, they had no independent prognostic value.     

A phase II trial of weekly infusional 5-fluorouracil in combination with low-dose leucovorin in patients with advanced colorectal cancer

We examined 59 breast cancers for p53 and bcl-2 protein expression by immunohistochemistry. The results were correlated with Ki-67 immunostaining. p53-negativity was noted in 40 cases and the remaining 19 tumours were p53-positive. Thirty-six tumours showed strong expression of bcl-2 and in 23 no staining for this protein was observed. We found statistically significant reverse correlation between expression of p53 and bcl-2 in majority of carcinomas: 31 cases were bcl-2 positive and p53-negative, and 14 tumours were bcl-2-negative and p53-positive. Six carcinomas showed no nuclear staining for Ki-67 and in the remaining 53 the percent of cancer cells positive for Ki-67 ranged from 1 to 60 (mean: 14.6). In these 53 cases we found that bcl-2-positive tumours were characterized by lower proliferation than bcl-2-negative tumours, the mean value of Ki-67 immunostaining being 10.7% and 23.0%, respectively. p53-negative tumours showed lower proliferation than p53-positive tumours: mean Ki-67 index was 10.2% and 23.9%, respectively. We conclude that immunohistochemically detected p53 and bcl-2 proteins show a significant inverse relationship in majority of breast carcinomas and their expression correlates with tumour proliferation (Ki-67 immunostaining).     

Hepatocellular proliferation and development of hepatocellular carcinoma: a case-control study in chronic hepatitis C

Patients with hepatitis C have an increased risk of developing hepatocellular carcinoma (HCC). This is related to the stage of chronic liver disease, as characterized histologically by hepatic fibrosis and architectural distortion, but it is unclear whether histological markers can define the risk of developing HCC. We conducted a case-control immunohistochemical study of Ki-67, a marker for hepatocellular proliferation, in livers of 18 patients who had developed HCC more than 2 years after the biopsy specimen had been taken. Using conditional logistic regression analysis, the results were compared with 18 selected controls, who were age-matched patients with hepatitis C of similar histological stage who had not developed HCC. We also examined livers for cellular dysplasia, p53 mutations, and bcl-2 overexpression, and assessed whether the results could be correlated with demographic and disease-related variables, such as gender, region of birth, alcohol consumption, severity of liver disease, HCV genotype, and markers of hepatitis B virus (HBV) infection. Livers from patients who developed HCC were more often positive for Ki-67 (13 of 18 [72%] v 9 of 18 [50%]; P = .06) and tended to have higher mean Ki-67 scores (6 +/- 7.5 v 3 +/- 4.4; P = .10) compared with control cases. In the HCC-predisposed group, three livers showed large cell dysplasia, two were positive for p53 mutations, and two for bcl-2 overexpression. In contrast, in the non-HCC group, only one case had dysplasia, and none were positive for immunostaining for p53 or bcl-2 mutations. With the exception of one case, all livers with large cell dysplasia or p53 mutations and bcl-2 overexpression were also positive for Ki-67. Twelve (55%) of the 22 Ki-67-positive cases were anti-HBc-positive in the serum, in contrast to 2 of 14 (14%) patients in the Ki-67-negative group (P = .01). Patients with evidence of past infection with HBV were more often Ki-67 positive than those who had no evidence of past infection (85% [11 of 13] v 45% [10 of 22]; P = .02). There were no other associations between demographic or disease-related variables and Ki-67 expression. Increased hepatocellular proliferative activity, as assessed by Ki-67 expression, may be one factor indicative of an increased risk of developing HCC among patients with chronic hepatitis C. Furthermore, past infection with HBV appears to be an important correlate of increased hepatocellular proliferation in hepatitis C.     

Paclitaxel-induced modification of the effects of radiation and alterations in the cell cycle in normal and tumor mammalian cells

Biopsy specimens from 12 patients with metastatic melanoma were longitudinally analysed to evaluate changes in proliferation activity and CD4+/CD8+ ratios during the course of the disease. The primary tumours of the patients who subsequently had metastatic disease were also each matched with tumours from two controls whose disease remained localized, and were compared with regard to tumour proliferation. Immunohistochemistry was performed using the avidin-biotin complex (ABC) immunoperoxidase technique, using bcl-2, p53, mdm-2 and Ki-67 as the primary monoclonal antibodies, and the percentage of positively stained melanocytic cells was calculated. Frozen sections were also available from metastatic lesions excised from eight of our patients before treatment initiation and at the time of disease progression. These specimens were prepared for microscopy, and quantitative characterization of CD4+ (OKT 4a) and CD8+ (OKT 8) cells was performed. Compared with the localized melanomas bcl-2 expression was higher in those primary melanomas that later metastasized (P = 0.068, Wilcoxon; P = 0.038, median test). Mdm-2 and Ki-67 expression did not differ in the primary tumours of patients and controls, but a statistically significant trend was observed towards increasing expression with the progression of the disease (two-sided exact P-values: 0.04 and 0.05, respectively). Patients with a low Ki-67 index in their first metastasis had a better prognosis when compared with patients with high indexes (P = 0.008, log-rank). Furthermore, most patients with decreasing CD4+/CD8+ ratios had increasing p53 immunoreactivity. Our findings suggest that Ki-67 and bcl-2 may be useful for predicting the prognosis of melanoma patients. Mdm-2 is a new but promising marker in melanoma and deserves further evaluation.     

Prognostic significance of bcl-2 protein expression in aggressive non-Hodgkin's lymphoma. Groupe d'Etude des Lymphomes de l'Adulte (GELA)

Little is known about the expression of bcl-2 protein in intermediate and high grade non-Hodgkin's lymphoma (NHL) and its clinical and prognostic significance. We performed immunohistochemical analysis of bcl-2 expression in tumoral tissue sections of 348 patients with high or intermediate grade NHL. These patients were uniformly treated with adriamycin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) in the induction phase of the LNH87 protocol. Fifty eight cases were excluded due to inadequate staining. Of the 290 remaining patients, 131 (45%) disclosed homogeneous positivity (high bcl-2 expression) in virtually all tumor cells, whereas 65 (23%) were negative and 94 (32%) exhibited intermediate staining. High bcl-2 expression was more frequent in B-cell NHL (109 of 214, 51%) than in T-cell NHL (6 of 35, 17%) (P = .0004), and was heterogeneously distributed among the different histological subtypes. Further analysis was performed on the 151 patients with diffuse large B-cell lymphoma (centroblastic and immunoblastic) to assess the clinical significance and potential prognostic value of bcl-2 expression in the most frequent and homogeneous immunohistological subgroup. High bcl-2 expression, found in 44% of these patients (67 of 151), was more frequently associated with III-IV stage disease (P = .002). Reduced disease-free survival (DFS) (P < .01) and overall survival (P < .05) were demonstrated in the patients with high bcl-2 expression. Indeed, the 3-year estimates of DFS and overall survival were 60% and 61%, respectively (high bcl-2 expression) versus 82% and 78%, respectively (negative/intermediate bcl-2 expression). A multivariate regression analysis confirmed the independent effect of bcl-2 protein expression on DFS. Thus bcl-2 protein expression, as demonstrated in routinely paraffin-embedded tissue, appears to be predictive of poor DFS, in agreement with the role of bcl-2 in chemotherapy-induced apoptosis. It might be considered as a new independent biologic prognostic parameter, which, especially in diffuse large B-cell NHL, could aid in the identification of patient risk groups.     

Automated and quantitative immunocytochemical assays of Bcl-2 protein in breast carcinomas

Expression of the bcl-2 gene was investigated in 218 human breast carcinomas by immunohistochemical analysis. Immunodetections were assessed using (1) frozen sections, (2) documented commercially available monoclonal antibody (bcl-2/124, Dako), (3) automation of immunoperoxidase technique (Ventana) and (4) quantitative evaluation of results by image analysis (SAMBA) and statistical analysis of quantitative data (BMDP software). Bcl-2 protein expression was correlated with current prognostic indicators and with molecular markers detected by the same procedure as for Bcl-2. It was shown that Bcl-2 expression is not related to patients' age, tumour size and type or lymph node status, but an inverse relationship was observed between Bcl-2 and tumour grade (P < 0.0001). An inverse relationship was also observed between Bcl-2 expression and p53 (P < 0.0001), Ki67/MIB1 antigen- (P = 0.0012), and P-gp- (P = 0.002) positive immunoreactions. In contrast, anti-Bcl-2 positive reaction was significantly associated with ER-positive (P < 0.001) and with ER/PR-positive or ER/PR/pS2-positive immunoreactions (P < or = 0.005). Bcl-2 expression was independent of CD31 and cathepsin D expression. Thus, Bcl-2 protein, thought to be antiapoptotic, exhibits parodoxical expression in human breast carcinomas. It is strongly detected in low-grade tumours (well-differentiated) with low (MIB1) growth fraction, but is independent of the tumour progression (size, node status, CD31, and cathepsin D). Bcl-2 acting on apoptosis is related to p53 gene abnormalities in breast carcinomas. Bcl-2 protein expression may also be involved in response to endocrine therapy (associated to ER/PR/pS2 positive immunoreactions) and probably with chemoresistance mechanisms (inverse relationship with P-gp).