乳腺癌细胞DNA含量分析及其预后关系

本实验应用流式细胞检测技术对53例乳腺癌石蜡包理组织标本DNA含量进行了测定,并分析了DNA倍体性、合成期细胞百分比与其他临床病理指标及患者5年存活率的关系,其中43例获得可供分析的结果.结果表明:(1)合成期细胞百分比(SPF)与患者5年存活率及腋淋巴结转移有显著相关性.(2)SPF和腋淋巴结转移与否结合可更准确地评估乳腺癌患者的预后.(3)DNA倍体性SPF、乳腺癌组织学类型之间无显著关系.作者认为:SPF反映了乳腺癌细胞的增殖活性和侵袭能力,可做为评估乳腺癌患者预后的指标.     

乳腺癌细胞DNA含量分析

本文应用流式细胞术(Flow Cytomotry简称FCM)测定41例乳腺癌细胞DNA含量,分析结果:DNA指数(DI)范围为0.9～2.91,其中二倍体肿瘤13例,占31.7％,异倍体肿瘤28例,占68.3％。DI和病理组织学分级呈正相关系,随着肿瘤组织学分级的增高,DI也升高。但是,在目前研究中,DI尚不反映临床分期。DI和预后的关系,共观察19例,发现二倍体肿瘤的预后好,生存期长,异倍体肿瘤的预后差,生存期短。本文应用针吸肿瘤细胞和切除标本新鲜组织块检测DNA含量,发现两种取材方法所得数值无显著差别。因此,认为针吸细胞应用FCM的DNA检查可作为术前辅助诊断方法,为治疗提供参考。     

乳腺癌组织中bcl-2蛋白表达及其与DNA倍体的关系

目的：探讨乳腺癌中bcl-2蛋白表达及DNA倍性与患者临床病理因素的关系，方法：采用流式细胞光度术(FCM)定量分析63例原发性乳腺癌癌组织、相应癌旁组织和22例乳腺良性肿瘤中bcl-2蛋白表达及DNA倍性结果：乳腺癌组织中bcl-2蛋白表达水平及DNA指数(DI)、S期比例(SPF)和增殖指数(PI)显著高于相应癌旁组织和乳腺艮性肿瘤(P＜0．05)，而后两者在上述指标上未见显著性差异(P＞0．05)。浸润性非特殊类型癌患者DI、SPF和Pl明显高于早期浸润癌患者和浸润性特殊类型癌患者(P＜0．05)；有淋巴结转移组患者DI和SPF显著高于无淋巴结转移组患者(P＜0．05)bcl-2蛋白表达与患者年龄、病理组织学类型、肿瘤大小、淋巴结转移、临床分期均无关(P＞0．05)癌组织bcl-2蛋白表达水平与SPF和PI呈负相关(P＜0．05)结论：bcl-2蛋白表达与乳腺癌发生、发展有关：DI和SPF与淋巴结转移有关；DNA含量可作为判断乳腺癌预后的重要指标     

Prognostic Significance of Lymph Node Status in Stage III Breast Cancer

Case histories of 103 patients with locally advanced (stage III) breast cancer have been reviewed. Ninety of the patients were judged operable. The median follow-up time was 52 months. The 5-year survival rate for the whole group was 54%. The 5-year relapse-free survival rates for the pN0, pN1 and pN2-3 were 91, 50 and 19% respectively and the 5-year survival rates for the groups were 86, 53 and 30% respectively. These results underline the heterogeneity and the very different prognoses for the different subgroups in stage III breast cancer patients. A reevaluation of the staging system is therefore suggested.     

Prognostic Factors in Locally Advanced Breast Cancer (T3, T4) with Special Reference to Tumor Cell DNA Content

The prognostic value of DNA analysis was studied retrospectively in 91 patients with locally advanced breast cancer (T3, T4) and a follow-up time of 3-7 years. Tumor cell DNA analysis was performed by static cytometry on aspiration biopsy specimens in 42 cases and on tissue sections in 49 cases. The tumors were classified as euploid or aneuploid. Sixty-four percent of the tumors were aneuploid. DNA pattern correlated significantly to histologic grade and axillary perinodal growth and also to survival. DNA pattern, histologic grade and axillary node metastases correlated significantly to disease-free survival (DFS). In this series of patients with locally advanced breast cancer DNA determinations gave important prognostic information.     

妊娠及哺乳期乳腺癌的治疗和预后

目的：总结70例妊娠及哺乳期乳腺癌的治疗和预后情况。其中Ⅰ期乳腺癌11例；Ⅱ期43例；亚期16例。结果：TNM分期、手术方式和治疗时间对病人的5年生存率有显著性意义（P＜0．05），是否终止妊娠则无显著性意义（P＞0．05）。本病治疗原则与一般乳腺癌相同，首选治疗方法是根治术或改良根治术，术后辅助放疗和化疗，其5年生存率分别为55．7％和74．3％，结论：终止妊娠不能提高病人生存率，目前尚无资料显示再次妊娠是否有害，Ⅰ期乳腺癌病人应在治疗2年后再考虑妊娠，Ⅱ、Ⅲ期乳腺癌病人预后较差，应避免再次妊娠或在治疗结束5年后再考虑妊娠。     

Circulating Cell Free DNA and DNA Integrity Index as Discriminating Tools between Breast Cancer and Benign Breast Disease

Objectives: Early diagnosis of cancer remains a great challenge in the field of laboratory medicine. We investigated the ability of ccf DNA and DNA integrity index (DNA II) in differentiating benign from malignant breast diseases. Methods: Serum samples were collected from 50 patients with benign breast disease (BBD) and 50 newly diagnosed breast cancer (BC) patients, in addition to 50 control women. VEGF was measured by ELISA, while Real-time q-PCR was used to measure ccf DNA concentrations and to assess the concentrations of ALU repeats, both short fragments (115 bp) and long fragments (247 bp), then DNA II was calculated (all were done before and after radical mastectomy). Results: BC group showed significantly higher ccf DNA concentrations and DNA II compared to BBD and control groups, meanwhile, no statistically significant differences were found between BBD and control groups. Ccf DNA concentrations decreased significantly after surgery (P <0.001). Good AUC was found for ccf DNA (AUC=0.860), fair AUC was found for DNA II (AUC=0.727), while VEGF AUC failed to discriminate between BBD and BC cases. Conclusion: ccf DNA and DNA II could be used as excellent molecular biomarkers for early diagnosis of BC and for monitoring the efficiency of therapy in such patients. Utilizing these molecular markers would improve both the healthcare and economic burden of malignancy.     

肺癌层粘连蛋白表达及DNA含量与预后关系的研究

对乙醇固定的３６例肺癌标本，采用ＰＡＰ法及流式细胞术（ＦＣＭ）进行层粘连蛋白（ＬａｍｉｎｉｎＬＭ）免疫组化测定和ＤＮＡ倍体及ＤＮＡ指数（ＤＩ）分析，并追踪随访６年。分析结果：ＬＭ阳性表达在组织学高分化组（１３／１９）高于低分化组（３／１７），二组间有显著性差异。也观察到同一病例不同部位ＬＭ表达有差异；本组异倍体率７７．１％（２７／３５），ＤＩ随癌组织分化程度的降低而增高；淋巴结转移组与无淋巴结转移组其ＬＭ表达及ＤＮＡ倍体分析未见显著性差异。随访结果：ＬＭ阳性组平均生存期（４１．４个月）明显高于ＬＭ阴性组（２８．１个月）（Ｐ＜０．０５）。５年以上生存组ＤＩ值１．２７９±０．１８明显低于５年以下组１．４１７±０．３２，二组有显著性差异（Ｐ＜０．００５）。作者认为：观察肺癌的ＬＭ表达与测定ＤＩ及ＤＮＡ倍体分析均有判断预后的意义。     

乳腺癌干细胞的调控及作用

乳腺癌是威胁妇女健康的重要疾病之一,由于其病因尚不完全清楚,目前还没有确切的预防方法,手术和放化疗是其主要的治疗办法,但其风险大且具有一定不良反应。研究发现,从实体肿瘤中分离出来的具有自我更新和多向分化能力的乳腺癌干细胞,能够介导肿瘤的侵入、转移和复发等过程,并且能够抵抗传统的放化疗,这对研究以乳腺癌干细胞为靶点的治疗方法具有重要的理论价值和实践意义。本文对乳腺癌干细胞的调控及作用的最新进展作一综述。     

三阴性乳腺癌的预后与上皮间叶转化的相关性

目的探讨三阴性乳腺癌的预后及与上皮间叶转化的关系。方法乳腺癌患者240例,根据ER、PR、Her-2的检测结果分为三组：三阴性组、受体阳性组和Her-2阳性组。原发灶石蜡标本制作组织芯片,免疫组织化学检测Vimentin的表达,比较三组的预后及Vimentin的表达差异。结果三阴性组的总生存及5年生存率均比受体阳性组差,和Her-2阳性组相比,差异无统计学意义。而三阴组的Vimentin阳性表达率明显高于受体阳性组或Her-2阳性组。结论三阴性乳腺癌的预后与上皮间叶转化有关。     

影响乳腺癌多发性癌灶发生的因素分析

目的：分析乳腺癌多发性癌灶发生的影响因素，方法：以获得病理诊断的乳腺癌组织标本118例作为研究对象，病理检查判断乳腺多发性癌灶的情况，针对患者的年龄，肿块的最大径，肿块距乳头的距离。病理类型，腋下淋巴结转移情况，有无脉管癌栓等因素进行单因素分析，将单因素分析得出的与多发性癌灶有关的4个变量，运用非条件logistic回归进行多因素分析，结果：患者年龄，肿块距乳头距离，肿块的病理类型是3个独立的因素，影响乳腺癌多发性癌灶的发生，结论：与其他情况相比，患者年龄在50岁以下，肿块距乳头距离≤2cm，病理类型是浸润导管癌或浸润性小叶癌，病理检查有脉管癌栓者易发生多发性癌灶。     

乳腺肿瘤增殖细胞核抗原与DNA定量的关系

目的用单克隆抗体对乳腺肿瘤细胞的增殖细胞核抗原ＰＣＮＡ进行免疫组化标记，并与细胞内ＤＮＡ定量，方法直方图周期分析加以比较。结果ＰＣＮＡ阳性细胞的分布在良性肿瘤及各级乳腺癌不同，其量的表达随恶性程度的增高而增高。经Ｘ２检验，Ｐ＜０．０２５，差异显著。结论ＰＣＮＡ中度和高度表达组的ＤＮＡ含量及异倍体率高于低表达组（Ｐ＜０．０５），但不是明显递增，而是在中度表达组中趋于最高。     

乳腺癌DNA含量与临床病理因素、PCNA关系

[目的]探讨乳腺癌DNA含量与临床病理因素及增殖指标PCNA的关系及其预后价值.[方法]利用图像分析技术测定90例乳腺癌DNA含量,SP法检测PCNA蛋白表达水平,多因素COX模型分析预后.[结果]90例乳腺癌异倍体率87.8%,低分化组乳腺癌DNA含量平均秩次高于高分化组(P＜O.05),DNA含量与PCNA相关系数为r=0.257,P＞O.05.DNA含量与PCNA均未进入COX方程中,淋巴结转移、年龄进入方程中.[结论]DNA含量可以反映乳腺癌的分化程度,对预后有参考价值.PCNA蛋白表达与DNA含量无相关性,两者均不是独立的预后因素.     

乳腺癌术前辅助化疗后原发肿瘤临床改变与预后

1971年1月～1982年12月,我院应用秋水仙硷制剂及CU方案术前辅助治疗可观察的乳腺癌390例,疗效达到CR18例,PR101例,SD259例,PD12例。5年生存率有效组(CR PR)与无效组(SD PD)分别为77.3％及65.7％(P=0.01),10年生存率两组分别为56.4％及50.9％(P=0.2)。肿瘤对化疗药物愈敏感,预后愈好,尤其是CR,腋结转移率为33.3％,5及10年生存率为94.4％及90.9％。当采用CU联合化疗时,原发瘤T_3,临床Ⅲ期及腋结转移时,5及10年生存率有效组较无效组有所提高,表明术前化疗对晚期病人可以改善预后。     

野生型PTEN基因在乳腺癌细胞中对表阿霉素的增敏作用

目的探讨野生型PTEN基因在人乳腺癌细胞系MCF-7和ZR-75-1中对表阿霉素的增敏作用。方法腺病毒介导野生型PTEN基因导入人乳腺癌细胞系MCF-7和ZR-75-1,RT-PCR检测PTEN mRNA的表达,Western blot检测转染后PTEN蛋白的表达;Ad-PTEN感染联合不同浓度的表阿霉素处理细胞,采用CCK-8法测定细胞增殖抑制率和联合效应。结果腺病毒介导的PTEN基因导入法可明显地增加细胞中PTEN基因的表达,野生型PTEN 基因转染联合表阿霉素使乳腺癌细胞MCF-7对表阿霉素的敏感度增加了两倍,而使乳腺癌细胞ZR-75-1对表阿霉素的敏感度增加了十倍。结论腺病毒重组的野生型PTEN基因联合表阿霉素对人乳腺癌细胞增殖具有显著的协同抑制效应。     

双调蛋白诱导乳腺癌细胞表达尿激酶型纤溶酶原活化物

目的:在人乳腺癌模型上研究双调蛋白与尿激酶型纤溶酶原活化物表达之间的关系.方法:乳腺癌NS2T2A1细胞经双调蛋白反义cDNA质粒转染后经潮霉素B筛选获得表达双调蛋白反义RNA的AR-AS1及AR-AS3两个细胞克隆,转染空载体获得NS2T2A1 V对照细胞,接种至裸鼠皮下形成肿瘤.测定细胞及肿瘤uPA表达水平,并研究uPA与细胞侵袭性之间的关系.结果:AR-AS1及AR-AS3细胞体外及体内uPA表达均被抑制.外源性双调蛋白可刺激对照细胞uPA的表达,并部分恢复AR-AS1及AR-AS3细胞uPA的表达水平.双调蛋白反义cDNA质粒转染及抗uPA抗体均导致乳腺癌细胞体外侵袭性的降低.结论:在乳腺癌模型上,uPA表达与肿瘤细胞的侵袭密切相关.双调蛋白反义RNA表达可有效地抑制uPA的表达,进而抑制肿瘤细胞的侵袭性.     

Circulating DNA in Egyptian Women with Breast Cancer

The commonest cancer in Egyptian females occurs in the breast cfDNA is a non-invasive marker for tumor detetion and prognostic assessment in many types of cancer including breast cancer. This study aimed to assess the role of cfDNA and its fragmentation pattern in breast cancer prognosis and treatment response. Forty female patients with malignant breast tumors and a comparable group of healthy blood donors were enrolled prospectively. cfDNA levels and fragmentation patterns were investigated after cfDNA extraction, gel electrophoresis and gel analysis. The percentage of breast cancer patients positive for cfDNA (92.5%) was significantly higher than that of controls (55%). Also, mean concentration of cfDNA was significantly higher than in the control group (P<0.05). Most Her-2 positive patients had long cfDNA fragments, this being significant as compared to Her-2 negative patients (P<0.05). Metastasis was also positively linked to significantly higher cfDNA (P<0.05) and the mean cfDNA integrity index was significantly higher in non-responders compared to treatment responders (P<0.05). In conclusion, both qualitative and quantitative aspects of cfDNA and its different fragments in breast cancer patients could be related to prognosis, metastasis and treatment response. Long cfDNA fragments could be particularly useful for prediction purposes.     

乳腺癌中雌激素受体与靶基因的结合预测内分泌治疗的敏感性观察

目的为提高乳腺癌患者内分泌治疗的敏感性,建立雌激素受体与靶基因结合活性的测定。方法使用凝胶阻滞方法,用γ-32P-ATP标记雌激素效应元件(ERE)作为探针检测89例乳腺癌组织中ER与靶基因DNA的结合活性。结果89例乳腺癌患者中50例ER(+)者中35例ERE(+),占70%;ER(+)、PR(+)的22例中18例ERE(+);而ER(-)患者中有7例为ERE(+)占ER(-)患者的18%。结论依照ERE的测定结果,结合ER,PR状态对临床乳腺癌的预后和抗激素治疗作出预测,并分为二大类Ⅰ类为ER(+)、ERE(+)、PR(+),这组患者预后较好,可优先考虑抗激素治疗Ⅱ类为ER(-)、ERE(-)、PR(-),抗激素治疗无效;ER(+)、PR(-)组依据ERE(+)归于Ⅰ类,ERE(-)归于Ⅱ类;对于ER(-)、PR(+)组ERE(+)为Ⅰ类,ERE(-)为Ⅱ类。经过这样的分类可增加科学性,减少临床用药的盲目性。