非霍奇金林巴瘤中细胞凋亡与细胞增殖的研究

目的 了解非霍奇金淋巴瘤（NHL）中细胞凋亡与细胞增殖间的关系，探讨两者在NHL发生与发展中的作用。方法 利用TdT介导的dUTP缺口末端标记（TUNEL）法和PCNA免疫组化技术原位检测60例NHL中的细胞凋亡和增殖水平，计算凋亡指数（AI）和增殖指数（PI）。结果 B细胞性NHL中，随着恶性度增高，AI和PI均增高（P＜0．05），T细胞性NHL中高度恶性组PI明显高于低度恶性组（P＜0．05），而AI在两组之间无显著性差异（P＞0．05）。AI和PI呈显著正相关（r=0．704，P＜0．01）。结论 在NHL中细胞凋亡与增殖之间可能存在密切的联系，共同参与了NHL的发生和恶性进展。对细胞凋亡和增殖水平的检测可能有助于NHL恶性度及预后的判断。     

胃癌病变演化中细胞凋亡与增殖及其与HSP70表达关系的临床生物学意义

目的研究胃癌和癌前病变中细胞凋亡与增殖,及其与热休克蛋白70(HSP70)表达的关系及临床生物学意义.方法应用免疫组织化学SP法检测158例胃粘膜病变石蜡标本中HSP70和增殖细胞核抗原(PCNA)的表达;并用DNA缺口末端标记法(TUNEL法)对其中56例标本进行细胞凋亡的原位观察.结果HSP70在胃癌中过表达,与不典型增生和肠上皮化生组相比有显著性差异(P＜0.05);细胞增殖指数PI在HSP70阳性表达组比阴性表达组显著增高(P＜0.01),但HSP70表达与细胞凋亡指数AI不相关;在慢性浅表性胃炎中AI明显较不典型增生组低(P＜0.01),随着病变的进展,胃癌中的AI逐渐降低,而PI则随病变的恶性进展不断升高.结论细胞凋亡和细胞增殖平衡失调在胃癌发病中起重要作用;HSP70的过度表达是胃癌发生过程中的早期事件,与细胞增殖相关密切,但与胃癌分化、淋巴结转移和浸润深度无关.     

介入化疗对宫颈鳞状细胞癌细胞凋亡和增殖的影响

目的:探讨介入化疗对宫颈鳞癌的细胞凋亡和增殖的影响.方法:选取宫颈鳞癌患者30例,介入化疗前后子宫组织,采用DNA缺口原位末端标记法(TUNEL)检测细胞凋亡,用凋亡指数(AI)表示;免疫组化染色SP法检测Ki67指数表达增殖变化,用LI表示;计算凋亡/增殖比例(AI/LI),并取30例正常宫颈上皮组织作为对照.结果:1)介入化疗后AI明显高于介入化疗前(P＜0.05).2)介入化疗后LI明显低于介入化疗前(P＜0.05).3)介入化疗前AI/LI(0.1293±0.079)低于对照组(0.2033±0.055),介入化疗后AI/LI(0.995 6±0.976)高于对照组,介入化疗后AI/LI明显高于介入化疗前,均有统计学意义(P＜0.05).结论:介入化疗能诱导宫颈癌细胞的凋亡,抑制宫颈癌细胞的增殖;AI/LI能表示细胞凋亡和增殖之间平衡.     

脑膜瘤DNA流式细胞术分析的临床病理学意义

目的探讨脑膜瘤细胞DNA倍体和增殖活性与脑膜瘤组织病理分型及生物学特性的关系.方法采用流式细胞仪检测42例脑膜瘤细胞DNA倍体和S期比例(SPF)、增殖指数(PI),结合肿瘤病理学类型进行相关性分析.结果在不典型、恶性脑膜瘤细胞中,非整倍体比例、SPF、PI显著性增高(P＜0.01);在组织亚型之间,各参数无显著性差异(P＞0.05):SPF、PI在非整倍体细胞系和复发脑膜瘤细胞中显著性增高(P＜0.01).结论流式细胞术分析是研究脑膜瘤细胞动力学和生物学特性的重要方法.DNA非整倍体可作为判定肿瘤恶性程度的指标.SPF、PI作为细胞增殖的指标,对脑膜瘤恶性程度和预后的评估具有重要意义.     

膀胱移行细胞癌中MDR、p53表达及细胞凋亡的意义

目的:探讨膀胱移行细胞癌(BTCC)中P-gP、p53基因及细胞凋亡表达的意义.方法:利用免疫组化S-P法和TUNEL法检测83例BTCC的P-gP、p53的表达及细胞凋亡指数(AI).结果:在83例膀胱移行细胞癌中P-gp阳性表达率为71.08%,p53阳性表达率为50.60%,AI为1.4335±0.3863;P-gp阳性表达在不同病理分级、临床分期及预后中无显著性差异(P＞0.05),p53及AI随着病理分级和临床分期而增高,均有显著性(P＜0.05),p53阳性表达复发组高于无复发组(P＜0.01),AJ复发组高于无复发组(P＜0.05).结论:检测P-gp可指导BTCC的化疗药物选择,p53高表达、细胞凋亡指数增高与BTCC的进展有关,P-gp、p53及AI高表达者预后及疗效差,p53可作为BTCC独立的预后因素.     

survivin在非小细胞肺癌中的表达及其与细胞凋亡的关系

目的:检测非小细胞肺癌(NSCLC)中survivin表达水平及凋亡指数(AI)大小,探讨其临床病理意义、在肺癌发生和进展中的作用以及二者可能存在的相关性.方法:应用免疫组织化学法检测108例NSCLC,60例癌旁肺组织survivin表达情况,原位末端标记法(TUNEL)检测AI大小.结果:survivin在NSCLC中表达高于癌旁肺组织(P＜0.05),NSCLC 中AI小于癌旁肺组织(P＜0.05),survivin表达及AI均与肿瘤组织的分化程度、TNM分期及淋巴结转移有关(P＜0.05),survivin表达与AI呈负相关(P＜0.05).结论:细胞凋亡水平异常可能在肺癌发生发展中起重要作用,survivin可能通过抑制细胞凋亡参与了肺癌的发生、发展.     

Cyclin D2在人脑胶质瘤的亚细胞表达及意义

目的研究细胞周期素D2(cyclin D2)在人脑胶质瘤中的亚细胞表达.方法采用免疫组化方法检测52例人脑胶质瘤及8例正常人脑组织中cyclin D2蛋白和增殖细胞核抗原(PCNA)的表达.结果正常人脑组织中无cyclin D2表达,而在胶质瘤细胞胞核和胞浆中均发现cyclin D2的阳性表达,并随肿瘤恶性程度增高而表达增强.其中11例(21.2%)出现胞核染色,高恶性度胶质瘤(Ⅲ～Ⅳ级)与低度恶性胶质瘤(Ⅰ～Ⅱ级)标记指数与阳性率无显著性差异(P＞0.05);胞浆染色阳性率为42.3%(22/52),低、高恶性度组标记指数间差异显著(P＜0.05),各相邻级别之间无显著差异(P＞0.05).二元相关性检验显示cyclin D2胞浆染色标记指数与PCNA标记指数呈正性相关(r=0.478,P＜0.01).结论人脑胶质瘤细胞胞核和胞浆中均存在cyclin D2的表达,其中胞浆表达与肿瘤细胞的增殖活性密切相关,提示其可能在肿瘤细胞细胞质中发挥重要正性调控作用.     

大肠癌组织中PCNA表达和细胞凋亡检测的临床意义

目的：探讨大肠癌组织中细胞凋亡和增殖细胞核抗原（PCNA）表达的临床意义。方法：应用免疫组化S－P法及TUNEL法对10例正常大肠黏膜和62例大肠癌组织中细胞增殖指数（PI）及凋亡指数（AI）进行检测，分析其与临床病理因素的关系。结果：在正常大肠黏膜和大肠癌组织中，PI逐渐增加，AI逐渐下降，两者比较有非常显著性差异（P＜0．01），随着大肠癌Dukes分期升高，PI逐渐增加，AI逐渐下降；与癌组织分化程度和淋巴结转移有关（P＜0．01），对这2种指标进行综合分析显示，PI增高而AI降低组，较其它异常结合模式组更易发生淋巴结转移。结论：细胞增殖与凋亡平衡失调的程度与大肠癌恶性程度密切相关，PI增高同时有AI降低者更易发生淋巴结转移，两者联合检测对大肠癌的临床分析及预后评价有重要意义。     

宫颈癌细胞凋亡和增殖与预后的探讨

目的 :探讨宫颈癌细胞凋亡、增殖与宫颈癌临床病理参数和预后的关系。方法 :利用TUNEL法和HE染色检测 5 0例宫颈癌组织 (鳞癌、腺癌各 2 5例 )的细胞凋亡指数 (AI)和核分裂指数 (MI)。结果 :腺癌的AI、MI明显高于鳞癌 (P <0 0 5 ) ,但AI MI指数比值两者差异有显著性。随着宫颈癌恶性级别增高、肿瘤体积的增大 ,AI、MI水平增高。AI与MI之间及AI MI的比值与宫颈癌 5年生存率之间有强的正相关性。结论 :宫颈癌细胞凋亡和增殖水平的增高与宫颈癌的恶化进展有关 ,同时检测AI、MI更有助于宫颈癌预后评价     

HK-Ⅱ在结肠癌组织中的表达及其临床意义

目的检测己糖激酶-Ⅱ(HK-Ⅱ)在人结肠癌组织中的表达,并探讨其与肿瘤细胞增殖、凋亡的关系及临床意义。方法采用免疫组织化学法检测68例结肠癌组织HK-Ⅱ和增殖细胞核抗原(PCNA)表达,采用脱氧核糖核苷酸转移酶介导的原位缺口末端标记 (TUNEL) 法检测细胞凋亡,计算增殖指数(PI)和凋亡指数(AI)。结果52例结肠癌组织HK-Ⅱ表达阳性,阳性率为76.5%。HK-Ⅱ阳性表达的结肠癌PI显著增高,而AI明显下降(均P<0.01)。结肠癌HK-Ⅱ表达在患者年龄、性别和肿瘤发生部位之间的差异无统计学意义(P>0.05);但在肿瘤分化程度、分期和淋巴结转移之间差异有统计学意义(P<0.05)。结论HK-Ⅱ在结肠癌增殖和进展中起着重要作用,可作为结肠癌恶性预后指标和临床治疗靶点。     

膀胱移行细胞癌中p53突变、bcl-2和PCNA表达的临床意义(英文)

目的探讨膀胱癌中 bcl-2、p53、PCNA 表达与细胞增殖、凋亡和临床病理学参数之间的关系。方法 SABC 免疫组化分折62例(T1G1-G339例,T2-T4aG3 NOM023例)甲醛固定和石蜡包埋的膀胱癌标本 bcl-2、p53和 PCNA 蛋白的免疫反应性。平均随访37个月,24例复发。增殖指数(PI)表示肿瘤细胞中 PCNA 阳性细胞百分比。TUNEL 法检测细胞凋亡,凋亡指数(AI)表示肿瘤细胞中凋亡细胞的百分比。结果 62例膀胱癌中,50例(80.0%)发生 p53突变,与 G1(72.7%)和 G2(78.5%)相比较 G3(91.3%)更多见(P<0.05);pT2期(95.7%)p53突变率较 pTa-1期(74.3%)高(P<0.01)。14例(22.5%)发现有 bcl-2表达,bcl-2表达阳性率 G3明显高于 G1和 G2(P<0.05),与分期无关(P>0.05)。Bcl-2表达与 p53突变无关。在膀胱癌中,PI 为17.2%～41.8%(平均为22.4%),AI 为1.9%～3.5%(平均为2.9%)。统计分析显示 PI 与肿瘤分级、分期关系密切,AI 与肿瘤的分级有明显关系。结论结果表明,p53突变与浸润性行为呈正相关。在膀胱癌中 p53和 PCNA 过表达可能能提供有价值的预后信息。随着肿瘤的进展,肿瘤细胞过度增殖可能伴有频繁的凋亡,但增殖指数的增加明显强于凋亡指数的增加。     

膀胱移行细胞癌中p53突变、bcl-2和PCNA表达的临床意义

目的　　探讨膀胱癌中bcl-2、p53、PCNA表达与细胞增殖、凋亡和临床病理学参数之间的关系。方法　　SABC 免疫组化分折62例(T1GI —G339 例,T2-T4aG3　NOM023例)甲醛固定和石蜡包埋的膀胱癌标本bcl-2、p53 和PCNA蛋白的免疫反应性。平均随访37个月,24例复发。增殖指数(PI)表示肿瘤细胞中PCNA阳性细胞百分比。TUNEL法检测细胞凋亡,凋亡指数(AI)表示肿瘤细胞中凋亡细胞的百分比。结果　　62例膀胱癌中,50例(80.0%)发生p53突变,与G1(72.7%)和G2(78.5%)相比较G3(91.3%)更多见(P<0.05);pT2期(95.7%)p53突变率较pTa-1期(74.3%)高(P<0.叭)。14例(22.5%)发现有bel-2表达,bcl-2表达阳性率G3明显高于G1和G2(P<0.05),与分期无关(P>0.05)。Bcl-2表达与p53突变无关。在膀胱癌中,PI 为17.2%～41.8%(平均为22.4%),AI为1.9%-3.5%(平均为2.9%)。统计分析显示PI与肿瘤分级、分期关系密切,AI与肿瘤的分级有明显关系。结论　　结果表明,p53突变与浸润性行为呈正相关。在膀胱癌中p53和PCNA过表达可能能提供有价值的预后信息。随着肿瘤的进展,肿瘤细胞过度增殖可能伴有频繁的凋亡,但增殖指数的增加明显强于凋亡指数的增加。     

结肠癌细胞凋亡与增殖的平衡及其与预后的关系

背景与目的:人体正常组织器官中,特定组织中凋亡与增殖细胞维持着动态平衡,一旦凋亡与增殖的平衡被打破,将导致细胞的恶性转化和肿瘤的发生。我们通过研究结肠癌细胞和淋巴细胞演进过程中凋亡与增殖平衡机制的变化,及其与患者生存的关系,探讨结肠癌的发生、发展规律。方法:采用低分子量DNA抽提后荧光染料染色法(Sub G1法)和Ki-67/DNA双参数法,分别定量分析凋亡群体和增殖群体。应用激光共聚焦显微镜对组织细胞的增殖进行形态学观察,Kaplan-M eier法分析生存率。结果:对照组细胞、腺瘤细胞、肿瘤组Dukes蒺A期、B期、C+D期细胞中,凋亡指数/增殖指数(apoptosis index/proliferating index,AI/PI)分别为0.45±0.19、0.30±0.07、0.29±0.11、0.28±0.10和0.26±0.07。对照组的AI/PI大于其余4组(P<0.01)。在结肠癌细胞的大小、类型、分化程度、Dukes蒺分期和淋巴结转移等临床病理特征中,AI/PI总体呈下调的趋势。正常人和肿瘤患者外周血淋巴细胞AI/PI分别为0.49±0.12和0.64±0.11。肿瘤患者淋巴细胞的AI/PI大于对照组(P<0.01)。用激光共聚焦显微镜可观察到结肠对照组、腺瘤和肿瘤组织中Ki-67的表达。根据AI/PI的中位数值0.285,将结肠癌患者分为≥0.285组和<0.285组。经log-rank检验两组患者生存时间无显著性     

Apoptosis and its correlation with proliferative activity in rectal cancer

BACKGROUND AND OBJECTIVES: Alterations in the normal control of apoptosis and cell proliferation are important factors in multistep colorectal carcinogenesis. The aim of this study was to determine the frequency of apoptosis and cell proliferation in rectal cancers and to examine their relationship to clinicopathological variables and expression of bcl-2 and p53. METHODS: Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining and immunohistochemical staining for Ki-67, bcl-2, and p53 were performed on paraffin-embedded tissue samples of 57 rectal cancers. RESULTS: There was a positive linear correlation between apoptotic index (AI) and proliferative index (PI) (gamma = 0.276, P = 0.038). Both apoptosis and cell proliferation were more frequently found in rectal cancers with lymph node metastasis (P = 0.045 and 0.010, respectively). However, the ratio of AI and PI was not different by nodal status. There was no association between Dukes stage and AI or PI. The frequency of apoptosis was inversely related to the expression of bcl-2, but was not related to the p53 status of rectal cancer. There were no association between cell proliferation and the expression of bcl-2 or p53. CONCLUSIONS: Our results suggest that the susceptibility to apoptosis in rectal cancer is clearly related to the proliferative activity and high turnover rate of tumor cells may contribute to lymph node metastasis.     

膀胱移行细胞癌中p53突变、bcl-2和PCNA表达的临床意义

To correlate the frequency of p53 mutations, bcl-2 expression and the proliferation status (proliferating cell nuclear antigen, PCNA) in patients with bladder cancer with cell proliferation, apoptosis and their clinico-pathologic findings. Paraffin-embedded sections from 39 superficial (T1G1-G3) and 23 invasive (T2-T4a G3 N0M0) primary transitional cell carcinomas (TCC) in the bladder were investigated immunohistochemically for p53, bcl-2 and PCNA. The median follow-up was 37 months; 24 had recurrences. The proliferation index (PI) was expressed as a percentage of the PCNA-positive cells in the tumor cells. Apoptosis was detected by terminal deoxy-nucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), and the apoptotic index (AI) was expressed as a percentage of the TUNEL-positive tumor cells. p53 mutation was identified in 50 patients (80.6%). The mutation was most common in tumors grade 3 (91.3%) as compared to grade 2 (78.5%) and grade 1 (72.7%, P<0.05). Stage pT2 tumors had a higher frequency of p53 mutation (95.7%) as compared to pTa-1 tumors (74.3%, P<0.01). Only 14 tumors (22.5%) expressed bcl-2; grade 3 tumors expressed bcl-2 significantly more frequently (P<0.05); there was no correlation between bcl-2 and tumor stage. There was no interrelation between p53 mutation and bcl-2 expression (P>0.05). The PI ranged from 17.2% to 41.8% (median 22.4%) and the AI from 1.9% to 3.5% (median 2.9%) in bladder cancer. Statistical analyses revealed a close associations between PI, AI and tumor grade and stage of bladder cancer. p53 mutation correlates with invasion. p53 and PCNA overexpression may offer valuable additional prognostic information in bladder tumors. With the progression of the tumor grade, cell proliferation may be accompanied by frequent apoptosis in bladder cancer, but the PI increased much more than the AI.     

Apoptosis in transitional cell carcinoma of bladder and its relation to proliferation and expression of P53 and Bcl-2

Transitional cell carcinoma of bladder (TCC) is a relatively common cancer among men. Tumor progression is associated with expression or modulation of several gene products that control apoptosis and proliferation. Apoptosis is a negative growth regulatory mechanism in tumors. The aim of this study is to examine apoptosis and related regulatory molecular markers in a group of patients with TCC. Paraffinembedded tissues from 49 patients with TCC were examined for the expression of bcl-2, p53 and Ki-67 by immunohistochemistry. Apoptosis was detected by TUNEL method. Correlation between apoptotic index (AI), proliferation index (PI) and bcl-2 and p53 expression with each other and with pathological grade was determined. Apoptosis was observed in 28.1% of TCC cases. The mean AI of all cases was 13.7+/-24. No correlation was found between apoptosis and differentiation status of carcinoma. Bcl-2 expression was weakly detected in only one sample. P53 expression was detected in 26 of cases with mean staining index of 102+/-96. A significant correlation between p53 and Ki-67 staining indices was observed (r=0.521, p=0.001). Both p53 and Ki-67 expression showed a good association with the pathological grade (p=0.0001 and p=0.004, respectively). None of the markers showed significant correlation with AI and no correlation was found between the ratio of AI to PI and other parameters either. In conclusion, the frequency of apoptosis in TCC of bladder appears not to be associated with tumor grade, and with bcl-2, p53 and Ki-67 expression.     

幽门螺杆菌感染性胃炎细胞凋亡与bcl-2/bax表达的意义

目的：探讨幽门螺杆菌ＨＰ引起胃粘膜上皮细胞凋亡和增殖发迹及ＨＰ致癌作用的可能机制。方法：采用免疫组织化学方法及脱氧核糖核酸末端转移酶介导的ｄＵＴＰ缺口末端标记（ＴＵＮＥＬ）技术,对ＨＰ阳性和ＨＰ阴性者胃粘膜上皮中增殖细胞,凋亡细胞进行原位观察和比较,同时检测ｂｃ１－２／ｂａｘ蛋白表达状态。结果：ＨＰ阳性者胃粘膜上皮细胞增殖指数和凋亡指数显著高于ＨＰ阴性者（Ｐ〈０．０１）。ｂａｘ蛋白表达阳性率在ＨＰ     

Survivin expression and its relation with proliferation, apoptosis, and angiogenesis in brain gliomas

BACKGROUND: An unbalance of cell proliferation and cell apoptosis is an important mechanism in carcinogenesis, and angiogenesis also plays a crucial role in tumorigenesis. Recently, survivin has been identified as an important member of the inhibitor of apoptosis protein (IAP) family. Although it has been shown that survivin is highly expressed in gliomas, and is associated with tumorigenesis, progression, and poor prognosis of gliomas, as yet the relation of survivin expression with proliferation, apoptosis, and angiogenesis of gliomas it is still unclear. METHODS: Eighty-three cases of brain glioma were chosen and protein expressions of survivin and proliferating cell nuclear antigen (PCNA) in glioma cells and Factor VIII-related antigen (FVIII-RAg) in vascular endothelial cells were investigated by immunohistochemistry. Apoptotic cells of brain glioma were screened by TdT-mediated dUTP nick end-labeling (TUNEL), and survivin immunoreactivity score (IRS), proliferative index (PI), apoptotic index (AI), overall daily growth (ODG), and microvessel density (MVD) in brain gliomas were measured. RESULTS: The survivin IRS, PI, AI, ODG, and MVD of brain gliomas were 3.75 +/- 3.89, 28.39 +/- 19.49%, 1.00 +/- 0.80%, 12.19 +/- 10.21%, and 62.75 +/- 31.50, respectively, and all of them increased markedly with an increase in the pathologic grade of brain gliomas (P < 0.001 for all). PI, ODG, and MVD in the survivin-positive group were significantly higher than those in the survivin-negative group (P < 0.001 for all). PI, ODG, and MVD were positively correlated with survivin IRS (P < 0.001 for all). Although there was no significant difference between AI in the survivin-positive group or in the survivin-negative group (P = 0.108), AI was inversely correlated with survivin IRS (P = 0.005). CONCLUSIONS: Survivin is overexpressed in brain gliomas, which may play an important role in malignant proliferation, antiapoptosis, and angiogenesis of brain gliomas.     

大肠癌组织COX-2的表达及其与肿瘤细胞增生和凋亡的关系

目的 探讨大肠癌中环氧化酶-2（c yclooxygenase-2,COX-2）表达及其与癌细胞增生和凋亡的关系.方法 采用免疫组织化学法检测60例大肠癌、20例大肠腺瘤和20例癌旁正常大肠黏膜中COX-2和PCNA的表达,并采用TUNEL法检测原位细胞凋亡水平.结果 大肠癌组织中COX-2阳性表达、PI及AI均显著高于大肠腺瘤及正常大肠黏膜组织（P＜0.05）;COX-2的高表达与大肠癌肿瘤大小、淋巴结转移和临床分期有关,与肿瘤生长部位、分化程度无关.COX-2阳性大肠癌组中PI高于COX-2阴性大肠癌组,AI低于COX-2阴性大肠癌组（P＜0.05）.结论 COX-2的过度表达可促进大肠癌细胞增生、抑制细胞凋亡,在大肠癌的发生、发展过程中起着重要的作用.     

Evidence of significant apoptosis in poorly differentiated ductal carcinoma in situ of the breast.

Following breast-conserving surgery for ductal carcinoma in situ (DCIS), the presence of comedo necrosis reportedly predicts for higher rates of post-operative recurrence. To examine the role of programmed cell death (apoptosis) in the aetiology of the cell death described as comedo necrosis, we studied 58 DCIS samples, using light microscopy, for morphological evidence of apoptotic cell death. The percentage of apoptotic cells (apoptotic index, AI) was compared between DCIS with and without evidence of ''comedo necrosis'' and related to the immunohistochemical expression of the anti-apoptosis gene bcl-2, mitotic index (MI), the cellular proliferation antigen Ki67, nuclear grade and oestrogen receptor (ER) status. AI was significantly higher in DCIS samples displaying high-grade comedo necrosis than in low-grade non-comedo samples: median AI = 1.60% (range 0.84-2.89%) and 0.45% (0.1-1.31%) respectively (P < 0.001). Increasing nuclear grade correlated positively with AI (P < 0.001) and negatively with bcl-2 expression (P = 0.003). Bcl-2 correlated negatively with AI (P = 0.019) and strongly with ER immunoreactivity (P < 0.001). Cellular proliferation markers (MI and Ki67 immunostaining) correlated strongly with AI and were higher in comedo lesions and tumours of high nuclear grade (P < 0.001 in all cases). Thus, apoptosis contributes significantly to the cell death described in ER-negative, high-grade DCIS in which a high proliferative rate is associated with a high apoptotic rate. It is likely that dysregulation of proliferation/apoptosis control mechanisms accounts for the more malignant features typical of ER negative comedo DCIS.