雌激素孕激素受体和人类表皮生长因子受体2在乳腺癌组织中的表达

目的 探讨雌激素受体(ER)、孕激素受体(PR)及人类表皮生长因子受体2(HER2)在乳腺癌中的表达及其与年龄、肿瘤大小、临床分期和腋窝淋巴结转移等的相关性.方法 对中山大学附属第一医院在2001年1月-2007年12月新收治的910例可手术乳腺癌的ER、PR、HER2及各种临床指标进行回顾性分析.结果 在910例的乳腺癌中,浸润性导管癌占89.4%,浸润性小叶癌占1.7%,导管原位癌占5%,其他类型占4.9%;肿瘤卣径<2 cm占29.9%,在2～5 cm之间的占45.6%,5 cm的占24.5%;无淋巴结转移的占54.2%,3个及3个以下淋巴结转移的占25.5%,4个及4个以上淋巴结转移的占20.3%.ER表达阴件的占33.0%,PR表达阴性的为27.4%.HER2表达为+++的占20.1%.随着患者年龄的增长,其就诊时淋巴结癌转移率减小(P＜0.001),其他指标与年龄无明显相关性;肿瘤大小与淋巴结痛转移率呈正相关(P＜0.001),与ER及PR的表达呈负相关(P＜0.001),与HER2表达呈正相关(P=0.02);ER与PR表达呈正相关(P＜0.001);ER及PR与HER-2呈明显负相关(P＜0.001).在不同淋巴结转移状态的乳癌中,ER、PR及HER2的表达差异无统计学意义.结论 ER、PR可作为乳腺浸润性导管癌预后良好的重要指标与HER2的表达呈负相关,HER-2的表达与年龄及淋巴结转移状态无明显的相关关系,临床上能更早期发现ER及PR阳性或HER2阴性的肿瘤.     

乳腺大汗腺癌临床和病理学特征研究

目的:探讨乳腺大汗腺癌(AC)的临床和病理学特征。方法:筛选出的8例乳腺大汗腺癌进行临床病理分析,采用过碘酸雪夫(PAS)、阿辛蓝(AB)染色及免疫组织化学A-P法检测GCDFP-15、Mucin-1、Ki-67、雄激素受体(Androgen receptor,AR)、雌激素受体(estrogen receptor,ER)、C-erbB-2。结果:8例均发生于中老年女性,因发现乳房包块就诊。组织学8例均为高级核,其中大汗腺导管原位癌(ADCIS)1例,ADCIS伴浸润性大汗腺癌(IAC)5例,IAC伴非大汗腺型DCIS灶2例。镜下主要有2种形态:A型,胞质嗜伊红染的粗颗粒状;B型,胞质淡染,呈细粉尘颗粒状,如毛玻璃样。8例AC的PAS染色阳性,AB染色在ADCIS阴性,在IAC可有50%细胞阳性,并同时表达GCDPF-15,AR,Mucin-1及Ki-67;除1例外,ER均不表达。结论:乳腺大汗腺癌的临床表现和大体形态与非乳腺大汗腺癌相似,多发生于单侧并且多数伴有同侧腋窝淋巴结转移,预后较好。其诊断主要依靠病理:(1)特征性的AC型细胞;(2)GCDPF-15阳性率高;(3)AR阳性率高,ER阳性率低。     

老年乳腺癌组织中雌激素受体、孕激素受体、人表皮生长因子受体2的表达及临床意义

目的:分析雌激素受体(estrogen receptor,ER),孕激素受体(progesterone receptor,PR),人表皮生长因子受体2 (human epithelial receptor-2,CerbB2)在老年女性乳腺癌中的表达情况,并探讨其临床意义.方法:回顾性分析125例老年乳腺癌患者的临床资料,免疫组织化学法检测ER,PR及CerbB2的表达情况,分析其与肿块大小、组织学分级、肿瘤部位以及淋巴结转移情况的关系.结果:ER,PR,CerbB2呈阳性表达者分别为84例(67.2％),83例(66.4％),25例(20.0％).ER,PR阳性表达与患者组织学分级相关,CerbB2阳性表达与患者肿块大小、组织学分级和淋巴结转移显著相关(P均＜0.01).3年及5年生存率分别为74.9％和62.0％,中位生存时间6.9年.结论:ER,PR在老年乳腺癌患者中阳性表达率高,而CerbB2阳性表达率低,联合检测三者表达可较好地反映老年乳腺癌病理生物学特征并指导手术治疗.     

乳腺大汗腺癌与雄激素受体表达的相关性

乳腺癌大汗腺癌是乳腺癌的少见类型,是一种激素依赖性肿瘤。乳腺大汗腺癌主要是由大汗腺分化的细胞构成的恶性肿瘤,在乳腺大汗腺癌中雄激素受体呈现高表达。目前很多实验研究发现,雄激素受体的表达与乳腺大汗腺癌的发生发展有着密切联系。     

乳腺浸润性大汗腺癌6例报道并文献复习

<正>乳腺大汗腺癌(Apocrine carcinoma, AC)是一种罕见的以大汗腺细胞形态为特征的特殊类型的乳腺癌,1916年由KROMPECHER首次描述^[1]。主要发生在高龄妇女,具有独特的形态学、免疫组化和分子遗传学特征,占女性所有乳腺浸润性癌的0.3%～4.0%^[2]。本文报道浸润性大汗腺癌6例,并结合国内外文献学习相关临床及病理特征、诊断、治疗以及预后。1 资料与方法1.1 病例资料收集长治医学院附属和平医院及山西医     

乳腺癌干细胞及其分化细胞中雌激素受体、孕激素受体和人类表皮生长因子受体2的表达

目的探讨乳腺癌干细胞及其分化细胞中雌激素受体(ER)、孕激素受体(PR)和人类表皮生长因子受体2(HER-2)的表达及意义。方法选取2016年1月至2016年10月新乡医学院第一附属医院标本室保存的新鲜乳腺癌标本35例,制备单细胞悬液,利用免疫磁珠分选法进行细胞分选,分选出乳腺癌干细胞(CD44~+CD24~-/low细胞)和分化细胞(CD44~-CD24~-细胞),利用Envision二步法检测乳腺癌干细胞及其分化细胞中ER、PR、HER-2的表达。结果同一患者的乳腺癌干细胞与分化细胞的ER、PR、HER-2表达呈现出3种情况:(1)乳腺癌干细胞阴性表达,分化细胞阳性表达;(2)乳腺癌干细胞阳性表达,分化细胞阳性表达;(3)乳腺癌干细胞阴性表达,分化细胞阴性表达。分化细胞中ER、PR及HER-2阳性表达率显著高于乳腺癌干细胞(P<0.05)。乳腺癌干细胞及其分化细胞共有4种表型,分别为SR~+HER-2~-、SR~+HER-2~+、SR-HER-2~+和SR-HER-2~-,其中,SR表示ER和(或)PR。乳腺癌干细胞的SR-HER-2~-表型比例最大,分化细胞的SR~+HER-2~-表型比例最大;分化细胞的SR~+HER-2~-、SR~+HER-2~+表型比例显著高于乳腺癌干细胞(P<0.05),分化细胞的SR-HER-2~-表型比例显著低于乳腺癌干细胞(P<0.05),但分化细胞与乳腺癌干细胞的SR-HER-2~+表型比例比较差异无统计学意义(P>0.05)。结论乳腺癌干细胞中ER、PR、HER-2阳性表达较低,随着乳腺癌干细胞的不断分化,阳性表达逐渐增加。     

表皮生长因子受体和C—erbB—2蛋白在人肝细胞癌中的表达

采用ＡＢＣ免疫组化方法，检测６８例人肝细胞癌中表皮生长因子受丛和Ｃ－ｅｒｂＢ－２蛋白的分布。发现ＥＧＦ－Ｒ的在正常肝组织中几乎不存在，而在癌旁肝组织和肝细胞癌中阳性百分比均显著增高；在低分化肝细胞癌中，ＥＧＦ－Ｒ的阳性百分比显著高于高分化肝细胞癌。     

表皮生长因子受体在人十二指肠溃疡的表达

采用免组化法检测了１１１例人十二指肠球部活检标本的表皮生长因子受体（ＥＧＦＲ）表达，结果表明ＥＧＦＲ表达以粘膜上皮细胞膜肠腔面最强，上皮细胞基侧膜和粘膜肌次之，上皮细胞胞浆又次，间质和十二指肠腺也有ＥＧＦＲ表达，淋巴滤泡无ＥＧＦＲ表达。ＥＧＦＲ表达在球部溃疡和溃疡瘢良有明显增强。ＥＧＦＲ表达强度与粘膜组织炎症程度有关，与性别、年龄无关。本次研究结果提示ＥＧＦＲ与粘膜组织对炎症的适应、溃疡的愈合和组     

浸润性乳腺癌组织中人表皮生长因子受体2表达的检测方法比较

目的:比较荧光原位杂交法(FISH)与免疫组化法(IHC)检测乳腺癌组织中人表皮生长因子受体2(HER2)基因扩增和蛋白表达的异同。方法:应用4B5 IHC法与FISH法对51例女性新发乳腺癌行HER2蛋白表达及基因扩增的检测,对结果进行统计分析。结果:2种方法检测HER2阳性率存在显著性差异(P<0.05);IHC法检测HER2蛋白0～1+与3+之间,通过FISH法检测HER2基因扩增的一致性好(κ=0.9,P<0.05);IHC检测HER2蛋白2+与3+之间与FISH法检测HER2基因扩增一致性良好(κ=0.777,P<0.05)。结论:4B5 IHC法与FISH法呈现很好的一致性。新的免疫组化抗体4B5检测HER2蛋白具有良好的灵敏度和稳定性。     

Effect of neoadjuvant chemotherapy on expressions of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and Ki-67 in breast cancer

Background This study was designed in an attempt to determine the influence of neoadjuvant chemotherapy on estrogen receptor （ER）, progesterone receptor （PR）, human epidermal growth factor receptor 2 （Her-2）, and Ki-67 expressions in patients with breast cancer. Methods Pre- and post-neoadjuvant chemotherapy, paired-tumor specimens from 103 patients with breast cancer administrated with anthracycline or anthracycline combined taxane regimen were collected. Immunohistochemical staining for ER, PR, Her-2, and Ki-67 was performed by the DAKO EnVision method. Results Among the 103 cases, five patients （4.9%） had a complete response （CR）, 82 （79.6%） partial response （PR）, 15 （14.6%） stable disease （SD）, and one （0.9%） progressive disease （PD）, yielding an overall response rate （CR ＋ PR） of 84.5%. Nine patients achieved pathological CR. There was a significant decrease in the average index of Ki-67 post- neoadjuvant chemotherapy, compared with that before chemotherapy （24.1% vs. 39.7%, P 〈0.001）. After neoadjuvant chemotherapy, the changes of Ki-67 in different subtypes of breast cancer were different （P 〈0.001）, and these changes correlated with response to neoadjuvant chemotherapy （P 〈0.001）. No significant changes in immunohistochemical expression were observed for ER, PR and Her-2. Conclusions Neoadjuvant chemotherapy apparently reduced Ki-67 index in primary breast carcinomas, but profiles for ER, PR and Her-2 were not significantly different before and after neoadjuvant chemotherapy. The change of Ki- 67 correlated with molecular subtypes and response to neoadjuvant chemotherapy, suggesting that Ki-67 index was a surrogate marker to predict the treatment response of neoadjuvant chemotherapy.     

表皮细胞生长因子受体测定及在肠癌的表达

本文报道灵敏、准确的表皮细胞生长因子(EGF)受体~(125)碘结合测定法.检测30例肠癌、癌周及正常肠组织 EGF 受体的表达。肠癌、癌周、正常肠组织 EGF 结合量分别为8.21±2.60(n=10),4.35±1.38(n=10)和1.41±0.43(n=10)fmol/mg膜蛋白,差异非常显著(P<0.01).Scatchard 作图,~(125)I-hEGF 结合是一条直线,肠癌 EGF 受体 KD 值25～315 fmol(n=9).     

乳腺癌α转化生长因子及表皮生长因子受体免疫组化双重标记研究

目的：研究α转化生长因子（TGFα）及其受体表皮生长因子受体（EGFR）在乳腺癌中的表达特点，以及两者间的相互作用。并通过与已知预后因素的相关分析，研究它们各自在肿瘤发展中的作用。方法：对84例导管浸润型乳腺癌标本进行TGFα－EGFR免疫组织化学双重标记，同时观察两者在非肿瘤及肿瘤组织的表达，并对结果进行单变量和多变量统计学分析。结果：TGFα和EGFR在癌旁组织上皮细胞中均有表达，分别在76．2％和17．8％浸润癌细胞中表达，在16．7％浸润癌细胞中同时表达。χ^2分析显示TGFα在浸润癌细胞中的表达只与ER阴性相关联，而EGFR的表达则与大体积肿瘤、炎性乳癌、腋窝淋巴结受累、不良肿瘤组织学分级（SBRⅢ级）以及雌孕激素受体阴性相关联。多变量统计分析显示，浸润癌细胞中TGFα的表达与炎性乳癌相关联（P＝0．048），而EGFR的表达则与雌激素受体阴性相关联（P＝0．002）。结论：TGFα和EGFR在乳腺癌组织中的表达与在非肿瘤组织中明显不同，并与乳腺癌不良愈后因素相关联，提示他们在乳腺癌的发展中起着重要作用。     

Prediction of recurrence risk in early breast cancer using human epidermal growth factor 2 and cyclin A2

Background Human epidermal growth factor 2 （HER2） is one of the most important prediction factors, but only 25%-30% of breast cancer patients HER2 are positive. It is unknown whether there are other molecular markers that could be used to predict prognosis and recurrence in HER2 negative patients.This study investigated correlations of cyclin A2 and HER2 levels with clinical outcomes in 281 patients with invasive breast cancer in order to identify whether cyclin A2 can serve as a prognostic factor in HER2 negative patients. Methods Immunohistochemical staining was used to detect cyclin A2 and HER2 expression in 281 patients. Cyclin A2 and HER2 gene amplifications were analyzed using gene analysis and RT-PCR in 12 patients. Risk and survival estimates were analyzed using Log-rank, Kaplan-Meier, and Cox regression analysis; cyclin A2 and HER2 consistency with survival were analyzed using Kappa analysis. Results Patients with higher cyclin A2 and HER2 expressions had significantly shorter disease-free survival periods （P=0.047 and P=-0.05, respectively）. Kappa analysis performed that cyclin A2 and HER2 showed a low Kappa index （kappa=0.37）, allowing us to conclude that cyclin A2 and HER2 detect different pathologies. Gene analysis and RT-PCR showed that cyclin A2 was upregulated in patients with early relapse; the average increase was 3.69-2.74 fold. Conclusions Cyclin A2 and HER2 are associated with proliferation and high recurrence, particularly when combined. Cyclin A2 is easily detected by nuclear staining and might be a useful biomarker for recurrence risk in HER2 negative patients.     

半乳糖凝集素3在乳腺癌中的表达及与人表皮生长因子受体2的关系

目的:研究半乳糖凝集素3（Galectin-3）在乳腺浸润性导管癌中的表达情况,探讨其与乳腺癌临床病理参数及人表皮生长因子受体2（Her-2）之间的关系。方法:收集70例乳腺浸润性导管癌组织,采用免疫组织化学法检测标本中Galectin-3、Her-2表达水平,对于Her-2 2+的组织进行荧光原位杂交检测。分析Galectin-3的表达与患者年龄、肿瘤大小、淋巴结转移情况、组织学分级、临床分期及Her-2的关系。结果:在不同年龄及肿瘤大小的乳腺癌组织中Galectin-3阳性率差异均无统计学意义（P>0.05）。淋巴结阳性组Galectin-3的阳性率高于淋巴结阴性组（P<0.05）;在不同组织分化程度及临床分期间Galectin-3的阳性率差异均有统计学意义（P<0.05）。乳腺癌组织中Galectin-3阳性率高于Her-2阳性率（P<0.05）。结论:Galectin-3在乳腺癌的发生、发展、侵袭和转移过程中发挥重要作用。检测乳腺癌组织中Galectin-3表达情况,有助于对肿瘤恶性程度及预后的判断,可能成为指导临床治疗的靶向指标之一。     

Comparison of immunohistochemistry with fluorescence in situ hybridization in determining the human epidermal growth factor receptor 2 status of breast cancer specimens: a multicenter study of 3 149 Chinese patients

Background Accurate detection of human epidermal growth factor receptor 2 （HER2） expression and gene amplification is crucial for the application of HER2-specific therapy and for evaluating the response of patients with breast cancer.A uniform and standard procedure of immunohistochemistry （IHC） and fluorescence in situ hybridization （FISH） needs to be established for evaluating the HER2 status in breast cancer tissues for the treatment of patients with real HER2-positive tumors.The present multicenter study was aimed to examine the HER2 status in breast cancer specimens from Chinese patients using both IHC and FISH methods.Methods A multicenter study was performed on the HER2 status in 3 149 breast cancer specimens from different ethnic populations and areas in China by IHC and FISH assays.The potential association of HER2 status with demographic and clinical characteristics was analyzed.Results The positive rates for HER2 over-expression and HER2 amplification were 23.3％ and 27.5％ in this study,respectively.The concordance between IHC and FISH was 71.2％ （K=0.494,P ＜0.001）.Furthermore,72.9％ of specimens with IHC 2＋ were negative to FISH.The discordance rates among laboratories were from 5％ to 28％ for IHC and 1％ to 16％ for FISH.HER2 amplification was associated significantly with advanced tumor stage （Ⅲ or Ⅳ,P=0.002）,large tumor size （＞5 cm,P=0.002）,moderate and poor histological grades （P ＜0.0001）,post-menopause （P ＜0.0001）,ER-PR-（P=0.002）,and having ＞4 lymph nodes affected （P ＜0.0001） in this population.The positive rates of HER2 amplification in specimens from Man and Hui Chinese were significantly higher than that in other Chinese populations.There are slightly higher positive rates of HER2 expression and amplification in Chinese patients with breast cancer.Conclusion These findings may provide new insights into understanding the epidemiological features of HER2 expression and amplification,and may be valuable for clinical practice.     

血管内皮生长因子、雌激素受体在甲状腺乳头状癌和甲状腺滤泡状腺瘤组织中的表达及其意义

目的:研究血管内皮生长因子(vascular endothelial growth factor,VEGF)雌激素受体(estrogen receptor,ER)在甲状腺乳头状癌和甲状腺滤泡状腺瘤及癌旁正常甲状腺组织中表达及意义,探讨两者对甲状腺乳头状癌治疗方案的制定和预后估计的临床意义。方法:对30例甲状腺乳头状癌、30例甲状腺滤泡状腺瘤和30例癌旁正常甲状腺组织,采用免疫组织化学S-P法,检测VEGF、ER表达。结果:VEGF、ER在甲状腺乳头状癌及甲状腺滤泡状腺瘤组织中的表达均有统计学意义(P<0.05),均高于癌旁正常甲状腺组织(P<0.05)。两者在甲状腺乳头状癌中的阳性表达率呈负相关关系(P<0.05)。结论:VEGF、ER的表达可作为甲状腺乳头状癌的协助诊断指标,是评价甲状腺乳头状癌和滤泡状腺瘤生物特性的重要指标,对临床治疗和预后判断具有重要的指导意义。     

Correlation of epidermal growth factor receptor overexpression with increased epidermal growth factor receptor gene copy number in esophageal squamous cell carcinomas

Background  Esophageal squamous cell carcinoma (ESCC) is one of the most frequent malignancies in China and epidermal growth factor receptor (EGFR) is widely distributed in human epithelial cell membrane. The aim of this study was to investigate the protein overexpression and gene copy number of EGFR in ESCC, and help to identify patients who may benefit from EGFR targeted therapies.  

Methods  Immunohistochemistry (IHC) was performed to analyze the expression of EGFR in 105 cases of ESCC, 16 cases of squamous epithelial atypical hyperplasia, and 11 cases of normal esophageal tissue. Fluorescence in situ hybridization (FISH) was performed to analyze the gene copy number in 80 cases of ESCC, eight cases of squamous epithelial atypical hyperplasia, and eight samples of normal esophageal tissue.

Results  The IHC-positive rates of EGFR in 105 cases of ESCC, 16 cases of squamous epithelial atypical hyperplasia, and 11 normal esophageal tissues were 97% (102/105), 44% (7/16), and 18% (2/11) respectively. The difference in the expression of EGFR among different esophageal tissue groups had statistically significance (P <0.05). Among the 105 cases of ESCC, overexpression of EGFR was found in 90 cases (86%), of which 55 cases scored 3+ for EGFR staining and 35 cases scored 2+. In ESCC, the expression of EGFR was significantly correlated with depth of invasion and TNM stage (P <0.05), but not with other parameters. The FISH-positive rates of EGFR in 80 cases of ESCC, the eight cases of squamous epithelial atypical hyperplasia, and eight samples of normal esophageal tissue were 31.3% (25/80), 0 (0/8) and 0 (0/8) respectively. In ESCC, EGFR gene amplification was found in 17 (21%) cases, high polysomy in 8 (10%) cases, disomy in 34 cases, low trisomy in 17 cases, and high trisomy in four cases. EGFR FISH-positive was significantly correlated with depth of invasion and lymph node metastasis (P <0.05). EGFR FISH-positive was significantly associated with overexpression of EGFR.

Conclusion  Protein overexpression and/or increased gene copy number of EGFR is common in ESCC, and EGFR targeted therapy may be appropriate for ESCC patients.

     

70例非小细胞肺癌表皮生长因子受体的检测分析

目的探讨表皮生长因子受体(EGFR)在非小细胞肺癌(NSCLC)中的表达特征及其临床病理意义。方法采用免疫组化染色Envision法检测EGFR在70例NSCLC中和12例健康肺组织中的表达。结果在70例NSCLC患者中,EGFR高表达率为72.9%,与健康肺组织比较差异有统计学意义(P<0.05),EGFR高表达与年龄、性别、肿瘤大小、组织学类型及病理分级间无关(P>0.05),与TNM分期、淋巴结转移显著相关(P<0.05),且其表达水平与TNM分期及淋巴结转移呈正相关。结论 (1)EGFR蛋白过表达与NSCLC的发生有密切关系;(2)EGFR蛋白过表达与NSCLC患者TNM分期及淋巴结转移相关,说明其过表达与肺癌的进展、转移有关。     

人脑胶质瘤中EGFR表达及微血管密度

目的：探讨表皮生长因子受体（EGFR）表达和血管生成在人脑胶质瘤发生发展中的作用以及EGFR表达与血管生成的关系。方法：采用免疫组化SABC和ABC方法分别检测63例人脑胶质瘤中EGFR和Ⅷ因子盯关抗原（FⅧRAg）的表达，计算微血管密度（MVD）。结果：高恶性度（Ⅲ-Ⅳ级）胶质瘤EGFR阳性率为83％，低恶性度（I－Ⅱ级）胶质瘤为58％，二者差异显著（P＜0．05）。EGFR表达随胶质瘤恶性程度增高而增强（P＜0．01）。高恶性度胶质瘤MVD高于低恶性度胶质瘤（P＜0．05）。胶质瘤MVD与EGFR表达呈正相关（γ＝0．899，P＜0．05）。结论：EGFR表达与血管生成是脑胶质瘤发生发展过程中的重要事件，EGFR具有促血管生成作用。