荧光原位杂交与免疫组化法检测乳腺癌HER-2表达的临床意义

[目的]探讨乳腺癌中荧光原位杂交(FISH)检测HER-2基因的扩增和免疫组织化学(IHC)检测HER-2蛋白表达在临床诊断及分子靶向治疗中的应用。[方法]采用FISH与IHC检测50例乳腺癌组织中HER-2基因的扩增与HER-2蛋白表达。[结果]50例浸润性乳腺癌中,FISH检测HER-2基因扩增阳性15例(30%),IHC检测HER-2蛋白表达(-～+)40例,HER-2蛋白表达(++)的2例,HER-2蛋白表达(+++)的8例。[结论]FISH检测HER-2基因的扩增与IHC检测HER-2蛋白表达(++～+++)有较高的一致性。对于IHC检测HER-2(-～++)表达时,必须进一步FISH检测。     

荧光原位杂交和免疫组织化学方法检测乳腺癌组织中人类表皮生长因子受体2基因状态差异及其特征分析

目的比较荧光原位杂交(fluorescence in situ hybridization,FISH)和免疫组织化学(immunohistochemistry,IHC)检测乳腺癌组织中人类表皮生长因子受体2(human epidermal growth factor receptor 2,HER-2)基因状态差异,分析其相关特征。方法回顾性收集51例中山大学附属第三医院2007年10月至2008年9月间乳腺浸润性导管癌组织标本和相关信息,分别采用IHC和FISH法检测HER-2蛋白表达情况和基因扩增状态,比较两种方法的结果差异,用Fisher精确概率检验分析这种差异的相关因素。结果在51例标本中,FISH检测乳腺癌组织中HER-2基因阴性32例(62.75%,32/51),阳性19例(37.25%,19/51);IHC检测乳腺癌组织中HER-2为(-)和(+)者的FISH检测均为阴性(21例);12例IHC检测HER-2为(++),其中3例FISH检测为阳性,其余9例FISH检测为阴性;18例IHC检测HER-2为(+++)者仍有2例FISH检测结果阴性。月经状态和雌激素受体(ER)表达与IHC检测HER-2阳性病例的FISH阳性结果具有显著联系(P值分别为0.023和0.007),即在IHC检测HER-2阳性[(++)和(+++)]的病例中,绝经前女性较绝经期女性以及ER阴性者较阳性者更可能为FISHHER-2阳性(有HER-2基因扩增)。结论本研究的结果有助于提高IHC判断HER-2基因扩增的准确性。     

荧光原位杂交与免疫组化检测乳腺癌组织HER-2基因扩增或蛋白表达情况的比较分析

目的 评估免疫组织化学(IHC)法检测乳腺癌组织中HER-2蛋白表达和荧光原位杂交(FISH)法检测其HER-2基因扩增在乳腺癌分子靶向治疗中的临床意义.方法 采用IHC法及FISH法分别检测47例乳腺癌组织中HER-2蛋白表达及HER-2基因扩增情况.结果 47例乳腺癌石蜡标本中,HER-2蛋白表达(+++)20例(42.55%),(++)10例(21.28%),(+)17例(36.17%);HER-2基因扩增22例(46.81%),无扩增25例(53.19%),其中17号染色体多体5例(10.64%).两种检测结果呈正相关(rs=0.415,P<0.05).结论 IHC法检测乳腺癌组织中HER-2蛋白表达町以作为是否应用赫赛汀的初筛;HER-2蛋白表达阳性的病例有必要进一步进行HER-2基凶扩增检测,来确定临床治疗是否应用赫赛汀.     

双色FISH分析浸润性乳腺癌HER-2基因扩增模式

[目的]应用荧光原位杂交技术(FISH)分析乳腺癌HER-2基因状态。[方法]采用双色FISH技术检测100例浸润性乳腺癌HER-2基因,分析FISH和免疫组织化学(IHC)检测结果,分析17号染色体多倍体比率及其与HER-2基因扩增的关系。[结果]100例浸润性乳腺癌标本中,HER-2蛋白IHC3+21例者中FISH检测均为阳性;IHC2+69例者中FISH检测为阳性的占72%,IHC1+10例者FISH检测为阳性的占20%。17号染色体多倍体的比率为51%。17号染色体二倍体与多倍体标本中,HER-2基因扩增的比率分别是76%和69%,差异无统计学意义(P=0.330)。[结论]乳腺癌IHC检测HER-2为1+~2+者需进一步行FISH检测确定HER-2基因状态;应用双色FISH方法能准确、全面评估HER-2基因状态。     

色素原位杂交法和免疫组织化学法检测乳腺癌HER-2基因扩增及蛋白表达

目的:对照色素原位杂交法(chromogenic in situ hybridization,CISH)和免疫组织化学法(immuno-histochemistry,IHC)检测乳腺癌组织中人表皮生长因子受体(human epidermal growth factor receptor-2,HER-2)基因扩增及其蛋白表达的状况.方法:采用CISH技术检测145例乳腺癌组织中HER-2的基因扩增情况,其中14例标本经过荧光原位杂交(fluorescence in si-tu hybridization,FISH)检测,随后分别用FISH和IHC方法检测的HER-2基因扩增及蛋白表达状况与之进行回顾性对照,并按照病理分级、淋巴结状态、绝经与否和雌激素受体(estrogen receptor,ER)/孕激素受体(progesterone receptor,PR)表达情况进行分层,分析HER-2表达与乳腺癌各高危因素之间的关系.结果:CISH检测发现,HER-2无扩增71例(50.0%),低扩增11例(7.6%),高扩增63例(43.4%).14例FISH与CISH检测结果比较,符合率为100.0%.145例IHC与CISH检测结果的符合率为84.8%(P<0.05).在IHC检测积分为0/ 以及 的病例中,HER-2基因扩增与蛋白表达情况基本一致,其符合率均在90%以上;而在IHC检测积分为 的标本中,HER-2基因扩增率仅为61.1%.CISH及IHC检测均显示ER/PR表达情况与HER-2阳性呈负相关,ER和PR均为阴性患者的HER-2基因扩增率和蛋白表达率明显高于ER/PR阳性的患者(CISH:68.3%vs 38.8%,P<0.01;IHC:71.7%vs 48.2%,P<0.01).HER-2状态与乳腺癌病理分级、腋淋巴结转移以及绝经与否无关(P>0.05).结论:CISH技术检测HER-2操作简便,准确性高,可以代替FISH技术,对IHC评分为 的病例应进一步确认HER-2状态.HER-2除了与ER/PR表达相关外,与其他乳腺癌高危因素无关,可作为独立指标进行检测.     

IHC和FISH检测乳腺癌HER-2表达的对比研究

目的:比较免疫组化(IHC)和荧光原位杂交(FISH)技术在检测乳腺浸润性癌患者中HER-2蛋白表达和基因扩增的一致性。方法:分别选用IHC和FISH技术对102例乳腺浸润性癌HER-2进行蛋白表达和基因扩增检测,比较两者检测的结果和相关性。结果:102例浸润性乳腺癌标本中FISH阳性55例,阴性47例。IHC检测0、1+、2+和3+的FISH阳性符合率分别为0(0/6)、9.52%(2/21)、65.00%(39/60)和93.33%(14/15)。IHC检测HER-2为2+/3+的标本中70.67%(53/75)显示HER-2基因扩增,1+/0患者中7.50%(2/27)显示HER-2基因扩增,Kappa系数为0.511,P<0.01。FISH检测结果显示,17号染色体多体总发生率为11.76%(12/102),在HER-2高表达的患者中发生率为9.33%(7/75),无或低表达发生率为18.52%(5/27),χ2=1.614,P=0.204。结论:HER-2蛋白表达和基因扩增IHC和FISH检测方法有较高的符合率,一致性较好。17号染色体多体可能是造成2种方法结果差异原因之一。     

应用荧光原位杂交法检测乳腺癌石腊样本中HER-2 基因的扩增

 目的 探讨荧光原位杂交法（Fluorescence in situ hybridization，FISH）检测乳腺癌HER-2基因扩增在临床病理诊断及分子靶向治疗中应用的可能性。方法 用FISH技术和免疫组化（Immunohisto—chemistry，IHC）技术检测50例乳腺导管癌石蜡包埋标本并比较两种方法的结果以及与临床病理的关系。结果 16／50例HER-2蛋白表达阳性，其中强阳性5例，中度阳性9例，弱阳性2例；11／50（22％）例乳腺癌标本FISH技术检测HER-2基因扩增阳性，其中5／5为免疫组化HER-2蛋白强阳性病例；6／9为中度阳性病例，其中1例为17号染色体多倍体与HER-2基因扩增。HER-2基因扩增与蛋白表达与乳腺癌转移有关（P〈0．05）。结论 FISH技术可稳定地检测用IHC确定的HER-2蛋白阳性乳腺癌中HER-2基因的扩增状况，并用于临床赫赛汀分子靶向治疗病例的筛选。     

荧光原位杂交和免疫组织化学法检测乳腺浸润性导管癌中HER-2基因状态的研究

目的 比较荧光原位杂交（FISH）和免疫组织化学（IHC）两种方法检测乳腺浸润性导管癌人类表皮生长因子受体2（HER-2）基因扩增及与C-erbB-2蛋白表达结果的一致性。方法 分别采用FISH和IHC法检测346例乳腺浸润性导管癌组织HER-2基因扩增和C-erbB-2蛋白表达,并对两种方法的结果进行统计学分析。结果 346例乳腺浸润性导管癌中,FISH检测HER-2基因扩增145例（41.9％）,无扩增201例（58.1％）。IHC检测显示,C-erbB-2蛋白（-）7例,（+）30例,（++）227例,（+++）82例。按乳腺癌HER-2检测指南,（-）和（+）为阴性结果,（+++）为阳性结果,（++）为不确定病例。全组IHC检测C-erbB-2蛋白阳性表达率为23.7％（82／346）。IHC检测C-erbB-2蛋白（-）的7例患者经FISH检测无HER-2基因扩增,一致率为100.0％。IHC检测C-erbB-2蛋白（+）的30例经FISH检测25例无基因扩增,一致率为83.3％;227例（++）中有65例基因扩增,一致率为28.6％;82例（+++）中有基因扩增75例,一致率为91.5％。IHC和FISH检测HER-2状态的一致率为89.9％,具有高度一致性（Kappa值=0.768,P＜0.001）。HER-2基因扩增与年龄、肿瘤大小、组织学分级及淋巴结转移均无关（P＞0.05）。结论IHC和FISH法检测乳腺浸润性导管癌HER-2表达状态有高度一致性。IHC可以作为初步筛查乳腺浸润性导管癌HER-2基因状态的首选检测方法,对于IHC检测结果为（++）的标本建议采用FISH法进一步明确HER-2基因扩增状态。     

荧光原位杂交法检测乳腺癌HER-2表达与腋淋巴结转移相关性的研究

目的:探讨用荧光原位杂交法(FISH)检测乳腺癌HER-2基因的表达与腋淋巴结转移的相关性.方法:采用免疫组化方法检测乳腺癌组织中HER-2的表达,再用FISH进一步检测阳性病例中HER-2基因的扩增情况,比较两者结果的差异,并且分析HER-2的表达与腋淋巴结转移的相关性.结果:免疫组化(IHC)法检测HER-2阳性42例,FISH检测阳性9例,FISH法检测HER-2基因与HER-2蛋白过表达之间相关(P＜0.05),并且IHC和FISH两种方法检测HER-2表达均与腋淋巴结转移有相关性(P＜0.05).结论:FISH可稳定检测HER-2基因的扩增,其表达与腋淋巴结转移相关.     

IHC、FISH与CISH检测乳腺癌Her-2基因状态的对比研究

目的 比较免疫组织化学法(IHC)、荧光原位杂交法(FISH)与显色原位杂交法(CISH)检测乳腺癌HER2基因状态的一致性,探讨FISH法与CISH法榆测乳腺癌HER2基因状态的临床意义.方法 对64例乳腺浸润性导管癌石蜡标本分别应用IHC法、CISH法与FISH法检测HER2蛋白、HER2基因状态及17号染色体多体的发生率.结果 HER2蛋白表达(+++)组,IHC与CISH、FISH法检测HER2基因扩增阳性的符合率均为100%;HER2蛋白表达(++)组,IHC与CISH、FISH法检测的符合率分别为95.83%与91.67%;HER2蛋白表达(+/-)组,IHC与CISH、FISH法检测的符合率亦均为100%.FISH法与CISH法的检测结果1例存在差异,FISH法与CISH法检测HER2基凶状态总的符合率为98.41%.17号染色体多体的发生率在IHC(+++、++、+/-)三组中分别为45.16%、45.83%和11.11%,其总的发生率为40.62%.结论 IHC法柃测HER2蛋白仅作为初筛方法;FISH法与CISH法检测HER2基因状态存在较高程度的符合率,CISH法可作为一种更加方便可行的方法检测HER2基凶状态;在疑有17号染色体多体干扰时,应进一步行FISH法检测.     

Bacteria and cancer--antagonisms and benefits

There is considerable historical and recent evidence concerning the antagonisms between acute bacterial infections or their toxins and cancer and allied diseases. These data provide renewed incentives to undertake clinical programmes with mixed bacterial vaccines in many countries at the present time.     

Religiosity and physical and emotional functioning among African American and White colorectal and lung cancer patients

The literature suggests that religiosity helps cope with illness. The present study examined the role of religiosity in functioning among African Americans and Whites with a cancer diagnosis. Patients were recruited from an existing study and mailed a religiosity survey. Participants (N = 269; 36% African American, 56% women) completed the mail survey, and interview data from the larger cohort was utilized in the analysis. Multivariate analyses indicated that in the overall sample religious behaviors were marginally and positively associated with mental health and negatively with depressive symptoms. Among women, religious behaviors were positively associated with mental health and negatively with depressive symptoms. Religiosity was not a predictor of study outcomes for men. Among African Americans, religious behaviors were positively associated with mental health and vitality. Among Whites, religious behaviors were negatively associated with depressive symptoms. These findings suggest a mixed role of religious involvement in cancer outcomes. The current findings may have applied potential in the areas of emotional functioning and depression.     

VEGF及KDR在大肠腺瘤和腺癌中的表达及意义

目的：探讨VEGF和KDR在大肠腺瘤和大肠腺癌中的表达及临床病理特征的关系。方法：大肠腺瘤和大肠腺癌组织标本各100例,采用免疫组织化学染色法检测VEGF和KDR在标本中的表达情况。结果：VEGF和KDR在大肠腺癌组中的阳性表达明显高于大肠腺瘤组（P〈0.05）;在正常大肠黏膜均未见VEGF和KDR表达的阳性染色;VEGF阳性表达组中KDR的阳性表达率为70%,显著高于VEGF阴性表达组中KDR的阳性表达率16%,两组比较有统计学意义（P〈0.01）。结论：大肠腺癌组织中KDR的表达与肿瘤大小、转移情况、浸润深度密切相关;VEGF和KDR在大肠腺瘤中的表达与患者的年龄、性别及分型均无相关性,而与增生程度相关（P〈0.05）。在大肠腺癌患者中VEGF及KDR表达更高,二者具有协同效应。     

Renal irradiation and the pharmacology and toxicity of methotrexate and cisplatinum

We used a rat model to study the effects of renal irradiation on the pharmacology of methotrexate (MTX) and cisplatinum (cis-Pt). Unanesthetized rats were given bilateral kidney irradiation (20 Gy in 9 fractions). At 9 months after irradiation, 3% of the animals had died and survivors showed moderately impaired renal function. At 15 months, 30% of the animals had died and survivors showed severely impaired renal function. Some animals were given i.v. MTX 1 week to 15 months after irradiation. In irradiated rats, the area under the MTX plasma clearance curve equaled that of controls through 6 months, and was significantly above controls from 9 months on. Other animals were given i.p. cis-Pt 1 week to 9 months after irradiation. The acute toxicity of cis-Pt was the same in control and irradiated rats when cis-Pt was given immediately before or after irradiation. Beginning 3 months after irradiation there was a progressive increase in cis-Pt toxicity and a simultaneous decrease in urinary platinum excretion. Irradiated animals that survived cis-Pt treatment showed increased radiation nephritis; the greatest effect occurred when cis-Pt was given 3 months or more after irradiation. MTX and cis-Pt clearance decreased when renal dysfunction was first observed and changes in renal function preceded changes in drug clearance and toxicity.     

Fruit and vegetables and cancer risk

The possibility that fruit and vegetables may help to reduce the risk of cancer has been studied for over 30 years, but no protective effects have been firmly established. For cancers of the upper gastrointestinal tract, epidemiological studies have generally observed that people with a relatively high intake of fruit and vegetables have a moderately reduced risk, but these observations must be interpreted cautiously because of potential confounding by smoking and alcohol. For lung cancer, recent large prospective analyses with detailed adjustment for smoking have not shown a convincing association between fruit and vegetable intake and reduced risk. For other common cancers, including colorectal, breast and prostate cancer, epidemiological studies suggest little or no association between total fruit and vegetable consumption and risk. It is still possible that there are benefits to be identified: there could be benefits in populations with low average intakes of fruit and vegetables, such that those eating moderate amounts have a lower cancer risk than those eating very low amounts, and there could also be effects of particular nutrients in certain fruits and vegetables, as fruit and vegetables have very varied composition. Nutritional principles indicate that healthy diets should include at least moderate amounts of fruit and vegetables, but the available data suggest that general increases in fruit and vegetable intake would not have much effect on cancer rates, at least in well-nourished populations. Current advice in relation to diet and cancer should include the recommendation to consume adequate amounts of fruit and vegetables, but should put most emphasis on the well-established adverse effects of obesity and high alcohol intakes.     

New and emerging radiosensitizers and radioprotectors

The combination of chemotherapy and radiation has led to clinical breakthroughs in several disease sites, and current work continues to define optimum combinations of proven chemotherapy as well as more recently available, noncytotoxic agents. Administration of systemic therapies allows modulation of radiation response to improve tumor control (radiosensitization) or to prevent normal tissue toxicity (radioprotection). Substantial progress has been made in identifying the targets of standard chemotherapeutic radiation sensitizers and protectors as well as in the introduction of a new generation of molecularly targeted therapies in combination with radiation. We have reviewed the most recent, predominantly early phase clinical trials combining systemic agents with radiation. Although the proof of an improved schedule ultimately needs to come from well-run Phase III trials, the search among schedules could be shortened by the use of surrogate endpoints such as presence of active drug metabolites in the tumor. This has been accomplished only in a few cases and needs to become a more standard part of radiation sensitizer and protector trials.