p16和人乳头瘤病毒检测在宫颈腺癌和宫内膜腺癌中的鉴别意义

目的探讨p16免疫组化染色和人乳头瘤病毒(HPV)DNA检测在鉴别宫颈腺癌(ECA)和子宫内膜腺癌(EMA)中的作用。方法 (1)采用免疫组化法检测41例ECA和72例EMA患者中p16的表达,采用着色范围和强度的半定量方法对结果进行评价,分析ECA和EMA患者中p16表达及与临床病理特征的关系。(2)杂交2代捕获法(HC-2)对41例ECA和46例EMA患者进行HPV DNA检测,分析二者的区别。结果 (1)p16在ECA和EMA的阳性率分别是97.5%(40/41)和80.6%(58/72),差异有统计学意义(P=0.009)。ECA患者中p16呈弥漫强阳性着色,EMA患者中则常呈局灶或斑片状着色。p16在ECA患者中的表达与淋巴结转移相关;p16在EMA患者中的表达与病理亚型、分化程度和国际妇产科协会(FIGO)分期有关。(2)ECA组中的HPV阳性率为22.0%(9/41),EMA组全部阴性,差异有统计学意义(P=0.001)。结论 p16和HPV检测对宫颈腺癌和宫内膜腺癌的鉴别有重要意义,可以为手术方式和治疗方案提供有价值的信息。     

子宫内膜样腺癌组织中内分泌细胞及其雌、孕激素受体的研究

目的　探讨子宫内膜样腺癌组织中内分泌细胞与雌、孕激素受体的关系。方法　采用免疫组化S -P法 ,检测 5 0例子宫内膜样腺癌组织中嗜铬素A(CgA )、雌激素受体 (ER )及孕激素受体 (PR )的表达情况 ,并对CgA阳性的子宫内膜样腺癌组织分别进行CgA /ER及CgA/PR双重免疫组化染色。 结果　子宫内膜样腺癌组织中CgA阳性率为 44 .0 % (2 2 /5 0 )。ER阳性率为2 8.0 % (14 /5 0 ) ,PR阳性率为 5 0 .0 % (2 5 /5 0 )。子宫内膜样腺癌CgA阳性组与阴性组之间ER表达率无显著性差异 (P >0 .0 5 ) ,但PR表达率有显著性差异 (P <0 .0 5 )。 2 2例CgA阳性子宫内膜癌细胞中CgA /ER同时表达率为 10 .1% (2 2 1/2 2 0 8个细胞 ) ,CgA/PR同时表达率为 2 0 .1% (4 90 /2 44 0个细胞 )。结论　子宫内膜癌组织出现较多的内分泌细胞及ER、PR的缺失是肿瘤异质性的表现。内分泌细胞不仅影响肿瘤细胞的生长 ,而且可能与子宫内膜癌对激素治疗的抗性或激素治疗后的复发有关     

雌激素和孕激素受体在胃癌中表达的意义

目的：应用相应单克隆抗体探讨胃癌中雌激素受体（ＥＲ）和孕激素受体ＰＲ表达的临床意义。方法：用ＥＲ、ＰＲ单克隆抗体对１２０例胃癌标本进行免疫组化（ＡＢＣ法）。结果：（１）ＥＲ、ＰＲ在１２例胃癌中阳性表达率分别为３２．５％、３０．８％；两者共同阳性３４例（２８．０％）；（２）ＥＰ、ＰＲ在胃癌Ｂｏｒｒｍａｎ第４型；胃低分化腺癌；粘液腺癌和有淋巴结转移组其阳性率明显高于其它各组（Ｐ〈０．０１）。而与患者年     

雌、孕激素受体与P-糖蛋白在肺癌中的表达及其意义

目的：探讨ER、PR、P—gP在肺癌组织中的表达情况，以及ER、PR与P—gP之间的关系，为肺癌的优化化疗、预测预后提供有价值的指标。方法：应用S—P免疫组化法检测石蜡包埋的肺癌标本中ER、PR、P—gP的表达。结果：P—gP阳性表达率36．05％(31／86)，ER、PR的阳性表达率分别为39．53％、41．86％，其中腺癌的表达明显高于其它组织类型。ER、PR的表达与肿瘤细胞分化水平呈正相关，而与患的性别、年龄、临床分期无关。31例P—gP阳性病例中，EP、PR阳性表达率为51．61％和64．52％，肺癌组织中P—gP与ER、PR的表达呈正相关。结论：P—gP与ER、PR之间可能存在某种相关性，提示肺癌的化疗若辅以性激素受体拮抗剂效果可能更好。     

子宫内膜癌组织雌、孕激素受体测定及其临床意义

目的:探讨子宫内膜癌组织雌激素受体(ER)和孕激素受体(PR)与临床病理特征的关系。方法:采用葡聚糖-活性炭吸附法(DCC法)对68例子宫内膜癌组织进行ER、PR测定,同时采用免疫组化法对其中30例进行ER、PR检测。结果:DCC法检测ER、PR的阳性率分别为79·4%和77·9%,免疫组化法均为86·7%。两种测定方法比较,ER与PR的总符合率分别为82·4%和85·7%。免疫组化法可在DCC法基础上进一步明确组织来源。ER、PR水平与组织学分级呈负相关。组织类型中腺癌(包括乳头状腺癌)与腺棘癌的ER、PR水平高于其他癌。ER水平与肥胖呈正相关。结论:ER、PR水平与组织学分级、组织学类型均反映了子宫内膜癌的生物学行为,ER、PR的测定对估计预后和临床选择激素治疗具有重要意义。     

ER PR和p16联合检测在子宫内膜腺癌和宫颈腺癌鉴别诊断中的应用

目的：探讨ER，PR和p16联合免疫组化染色在子宫内膜腺癌和宫颈腺癌鉴别诊断中的价值。方法：采用免疫组化SP法染色，观察ER，PR，p16在子宫内膜腺癌和宫颈腺癌中的表达情况。结果：子宫内膜腺癌中ER，PR和p16的阳性率分别为85．29％、76．47％、23．52％；宫颈腺癌为33．33％、42．86％、80．95％，子宫内膜腺癌ER，PR的阳性率明显高于宫颈腺癌，宫颈腺癌p16的阳性率明显高于子宫内膜腺癌。在子宫内膜腺癌和宫颈腺癌中3种标记差异均有显著性（ER：χ^2=20．78P〈0．005；PR：χ^2=8．32P〈0．01；p16：χ^2=17．24 P〈0．005）。结论：ER，PR，p16联合检测对鉴别子宫内膜腺癌和宫颈腺癌有一定实用价值。     

肺肿瘤与雌激素关系及治疗探讨

目的研究雌激素、雌激素受体(ER)、孕激素受体(PR)与人类肺恶性肿瘤发生、发展之间的关系,探讨肺肿瘤内分泌治疗的可能性。方法利用组织化学技术检测56例肺肿瘤组织标本ER、PR表达,然后应用典型的雌激素受体拮抗剂-他莫昔芬(tamoxifen)治疗受体表达阳性的且化疗无效的晚期肺肿瘤患者16例,观察其治疗效果及副作用。结果人类自然发生的肺肿瘤细胞含有ER、PR,其阳性率分别为42.9%和30.4%;腺癌ER、PR的阳性率71.4%和35.7%明显高于鳞癌的31.0%和17.2%(P<0.05);ER与PR的表达明显正相关(P<0.05);自化疗开始1~3疗程无进一步改善的肺癌者16例,TAM治疗后7例缓解或稳定,生存期8~24个月,平均14个月。TAM治疗无明显毒副作用。结论部分肺肿瘤细胞含有ER、PR,意味着这些肿瘤有雌激素依赖性,其发生、发展可能受雌激素调控,内分泌治疗有效;晚期肺癌患者如果ER、PR阳性,加用雌激素受体拮抗剂可能会有一定效果;TAM对临床难治性、ER阳性的肺癌有一定疗效且毒副作用不大,可在临床进一步试用。     

p53蛋白、雌激素受体、孕激素受体在非小细胞肺癌中的表达及临床意义

目的 检测非小细胞肺癌（ＮＳＣＬＣ）中ｐ５３蛋白、雌激素受体（ＥＲ）和孕激素受体（ＰＲ）表达与临床病理和预后的相关性。方法 应用免疫组织化学ＳＰ法检测１４７例ＮＳＣＬＣ癌组织标本中ｐ５３、ＥＲ、ＰＲ的表达。结果 ｐ５３蛋白总阳性率为６１．２％（９０／１４７）,鳞癌、腺癌、鳞腺癌、大细胞癌阳性率分别为６３．５％（４０／６３）、５７．６％（３３／６６）、６６．７％（１０／１４）、５０％（２／４）。腺癌     

Effect of neoadjuvant chemotherapy on breast cancer phenotype,ER/PR and HER2 expression – Implications for the practising oncologist

PurposeTo assess the effect of neoadjuvant chemotherapy (NACT) on breast cancer characteristics, hormone receptors and human epidermal growth factor receptor 2 (HER2) expression and whether testing should be repeated on residual tumours.Material and methodsPatients with primary operable breast cancer who received NACT at a single United Kingdom tertiary referral centre were included. Tumour type, grade (including details of mitotic grade, tubule formation and pleomorphism), oestrogen receptor (ER), progesterone receptor (PR) and HER2 status were compared between pre-treatment and post-treatment residual samples using tissue microarrays. A control group of paired core and excision tumours from patients who did not receive NACT was also assessed.ResultsTwo hundred forty-six cases and 113 controls were included. Pathological complete response (path CR) was achieved in 21.5% of patients. In those patients failing to achieve a path CR, a change in the histological type was noted in 29 out of 178 cases (16.3%, p < 0.001) with increase in the lobular and metaplastic types. Downgrading occurred in 28.8%, due to significant reduction in mitotic rate and prominent tubule formation. A change in ER/PR/HER2 status occurred in 12%, 14.5% and 7.1% of cases, respectively, predominantly as a switch from negative to positive status for ER and from positive to negative status for HER2. Further alterations in expression levels were also noted. Minimal changes in the low ER/PR expressors and the HER2 2+ tumours were found in the control group.ConclusionSignificant changes in tumour morphology, grade, hormone receptors and HER2 status occur following NACT. We recommend testing on residual invasive carcinoma. A switch from negative to positive status warrants offering endocrine/trastuzumab-based therapy to this group of patients.     

分化型甲状腺癌组织中雌激素受体和孕激素受体表达的临床意义

  目的  探讨分化型甲状腺癌是否为女性激素依赖性肿瘤，分析ER、PR的表达与分化型甲状腺癌患者的肿瘤大小、组织学类型、有否淋巴结转移、性别、年龄等的关系。  方法  应用免疫组织化学方法（SP法）检测分析正常甲状腺、甲状腺良性肿瘤和分化型甲状腺癌组织中ER、PR的表达。  结果  分化型甲状腺癌中ER和PR阳性表达分别为19.3%（10/52）和30.8%（16/52），其表达比正常甲状腺与良性肿瘤组织多，有显著性差异（P < 0.01）。分化型甲状腺癌的肿瘤直径>1 cm的ER、PR阳性率明显高于≤1 cm的病例，有显著性差异（P < 0.01）。而ER和PR的表达与患者的性别、年龄、组织类型和淋巴结转移无关。  结论  分化型甲状腺癌组织中ER和PR的表达较正常甲状腺、甲状腺良性肿瘤组织高，有显著差异性（P < 0.01），且肿瘤直径>1 cm者的ER和PR表达高于肿瘤直径≤1 cm者，揭示分化型甲状腺癌可能是雌激素和孕激素依赖性肿瘤。      

Discordance in ERα, PR and HER2 receptor status across different distant breast cancer metastases within the same patient

BackgroundWe studied discordance in estrogen receptor alpha (ERα), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status between multiple distant metastases from the same breast cancer patient.Material and methodsMultiple distant metastases from 55 female patients were stained for ERα, PR and HER2 by immunohistochemistry and in situ hybridization for confirmation of the HER2 status.ResultsDifferent metastatic sites within the same patient showed discordance in ERα receptor status in 7.3% or 10.9% of patients (using a 10% or 1% threshold for positivity, respectively). For PR, 29.1% or 30.9% of patients showed discordance. Taking ERα and PR together, 36.4% of cases (both thresholds) showed discrepancy between metastases. In 10.9% (10% threshold) or 14.5% of patients (1% threshold), such discordance could have clinical consequences with regard to hormonal treatment. For HER2, there was 3.6% discordance on the immunohistochemical level but 0% on the gene level.ConclusionIn a significant proportion of metastatic breast cancer patients, discordance in ERα and PR receptor status between different metastatic sites was observed. This implies that multiple metastases may need to be biopsied to optimally reassess receptors.     

Prognostic impact of discordance between triple-receptor measurements in primary and recurrent breast cancer

BackgroundWe evaluated discordance in expression measurements for estrogen receptor (ER), progesterone receptor (PR), and HER2 between primary and recurrent tumors in patients with recurrent breast cancer and its effect on prognosis.MethodsA total of 789 patients with recurrent breast cancer were studied. ER, PR, and HER2 status were determined by immunohistochemistry (IHC) and/or FISH. Repeat markers for ER, PR, and HER2 were available in 28.9%, 27.6%, and 70.0%, respectively. Primary and recurrent tumors were classified as triple receptor-negative breast cancer (TNBC) or receptor-positive breast cancer (RPBC, i.e. expressing at least one receptor). Discordance was correlated with clinical/pathological parameters.ResultsDiscordance for ER, PR, and HER2 was 18.4%, 40.3%, and 13.6%, respectively. Patients with concordant RPBC had significantly better post-recurrence survival (PRS) than discordant cases; patients with discordant receptor status had similarly unfavorable survival as patients with concordant TNBC. IHC scores for ER and PR showed weak concordance between primary and recurrent tumors. Concordance of HER2–FISH scores was higher.ConclusionsConcordance of quantitative hormone receptor measurements between primary and recurrent tumors is modest consistent with suboptimal reproducibility of measurement methods, particularly for IHC. Discordant cases have poor survival probably due to inappropriate use of targeted therapies. However, biological change in clinical phenotype cannot be completely excluded.     

乳腺增生病雌、孕激素受体表达及临床意义

目的:探讨乳腺增生病变组织中雌、孕激素受体表达情况,及其临床意义。方法:将乳腺增生病患者手术切除标本,常规福尔马林固定,石蜡包埋,采用免疫组化S-P法,测定ER、PR表达。结果ER和PR总阳性率74.36%(27/39)和87.18%(34/39),ER、PR同时阳性为66.67%(26/39)。本组不典型增生6例ER和PR阳性率均为100%,其表达强度最强,其次为腺病伴腺瘤形成,最弱为小叶增生。结论:乳腺增生病变组织中ER、PR虽然呈高表达,是三苯氧胺(TAM)治疗的适应症,但仍有25.64%的患者ER呈阴性表达,因此,用TAM治疗乳腺增生病前应检测患者的ER和PR,阳性者可用TAM治疗。     

子宫内膜癌雌、孕激素受体和C-erbB-2检测的临床意义

目的 检测子宫内膜癌组织中雌激素受体(ER)、孕激素受体(PR)及癌基因蛋白C-erbB-2表达的阳性率并探讨其与预后的关系.方法 用免疫组织化学法对32份子宫内膜癌标本进行了ER、PR及C-erbB-2的检测.结果 子宫内膜癌组织中ER、PR、C-erbB-2的阳性率分别为53.1%、50.0%、46.9%.ER、PR的阳性表达率与癌组织的细胞分化程度有关,随着子宫内膜癌组织学分级的增高,ER、PR阳性表达率逐渐降低,C-erbB-2的阳性表达率与肿瘤病理分级呈正相关,与ER、PR表达呈负相关.结论 ER、PR、C-erbB-2均反映了子宫内膜癌的生物学行为,其测定对预测预后、指导选择内分泌治疗具有重要意义.     

乳腺浸润性微乳头状癌临床病理特征及其预后分析

目的:探讨乳腺浸润性微乳头状癌（invasive micropapillary carcinoma ，IMPC）的临床病理特征及预后分析。方法:回顾性分析河北医科大学第四医院2009年1 月至2011年12月确诊的65例乳腺IMPC 患者，采用免疫组织化学法检测上皮膜抗原（epithelial membrane antigen ，EMA）表达以确定微乳头成分在肿瘤中所占比例。按微乳头比例≤ 10% 、11% ～30% 、31% ～50% 、> 50%将患者分为4 组，并同时检测ER、PR、HER-2 的表达。Kaplan-Meier 单因素生存分析中行Logrank 检验，采用多因素Cox 风险回归模型行生存时间的影响因素分析。结果:65例乳腺IMPC 患者中单纯IMPC 12例，IMPC 伴浸润性导管癌46例，IMPC 伴其他浸润性癌7 例。乳腺IMPC 中微乳头比例≤ 10% 组为7.69%（5/ 65）、11% ～30% 组为44.62%（29/ 65）、31% ～50% 组为26.15%（17/ 65）、>50% 组为21.54%（14/ 65），4 组乳腺IMPC 患者中淋巴结转移阳性率差异具有统计学意义（P < 0.01）。 免疫组织化学法结果显示，ER、PR和HER-2 在乳腺IMPC 组织中的阳性率分别为76.92%（50/ 65）、67.69%（44/ 65）和24.62%（16/ 65），差异具有统计学意义（P < 0.05）。 Kaplan-Meier 单因素分析显示患者生存时间与淋巴结转移数，微乳头比例，脉管瘤栓，ER、PR、HER-2 的表达相关（P <0.05）。结论:淋巴结转移数，微乳头比例，脉管瘤栓，ER、PR及HER-2 的表达均与乳腺IMPC 的预后相关。      

Prognostic Significance of HER2 Expression Changes Following Neoadjuvant Chemotherapy in Saudi Patients With Locally Advanced Breast Cancer

BackgroundProgesterone receptor (PR), estrogen receptor (ER), and human epidermal growth factor receptor 2 (HER2) significantly influence disease prognosis and therapeutic response in patients with breast cancer. Neoadjuvant chemotherapy (NACT) can change the receptor status, affecting the disease characteristics.Patients and MethodsA retrospective chart review was carried out at a single tertiary care hospital in Riyadh, Kingdom of Saudi Arabia, from December 2008 to December 2014, where 91 adult female patients diagnosed with locally advanced breast cancer planning to receive NACT were included. Original pathology and surgical histopathology reports were assessed, and patients were followed up to recurrence, death, or until December 2019. An expression for the ER, PR, and HER2 was carried out in pre and post NACT specimens by an experienced pathologist, and all HER2 with 2+ immunohistochemistry was sent for fluorescence in situ hybridization as per American Society of Clinical Oncology guidelines.ResultsER pre- and postoperatively changed from positive to negative in 17.6% of patients and from negative to positive in 1.1% of patients (P < .001). ER status remained stable in 81.3% of patients. PR changed from positive to negative in 13.2% of patients, and from negative to positive in 3.3% of patients (P < .001), whereas it remained stable in 83.5% of patients. HER2 changed from positive to negative in 11% of patients, and from negative to positive in 5.5% of patients (P < .001), and it remained stable in 83.5% of patients. No significant association was found between overall survival and disease-free-survival with HER2 expression change.ConclusionNACT can induce changes in the ER, PR, and HER2 status, which should be evaluated post-NACT to choose the optimal treatment regimens.     

性激素受体及调节蛋白在胃腺癌组织中的表达及其意义

目的：检测雌激素受体（ER）,孕激素受体（PR）,雄激素受体（AR）及雌激素调节蛋白（PS2）在30例胃腺癌组织中的表达情况,探讨其表达与临床治疗预后的关系。方法：采用免疫组化LSAB法进行检测,结果：ER,PR和AR的阳性率分别为53．3％,60％和16．7％,其表达在不同的组织类型及不同的分化程度之间均无明显差异（P＞0．05）,PS2的阳性率为53．33％,在有粘液分泌组的胃腺癌中的表达显高于无粘液分泌组（P＜0．05）。结论：胃腺癌具有较强的合成性激素受体的能力,对性激素的依赖性较大,临床可给予相应的抗性激素的治疗,PS2的表达对判断胃腺癌的预后有重要意义。     

免疫组化标记物在子宫内膜样腺癌与宫颈腺癌鉴别诊断中的表达及意义

目的探讨免疫组化标记物波形蛋白(Vimentin)、癌胚抗原(CEA)、雌激素受体(ER)、孕激素受体(PR)和p16蛋白在子宫内膜样腺癌与宫颈腺癌鉴别诊断中的表达和意义。方法采用免疫组织化学染色法检测48例子宫内膜样腺癌和21例宫颈腺癌患者肿瘤组织中Vimentin、CEA、ER、PR和p16的表达,并分析其临床意义。结果子宫内膜样腺癌患者肿瘤组织中Vimentin、CEA、ER、PR和p16阳性表达率分别为79.2%、31.3%、87.5%、81.3%和20.8%。宫颈腺癌患者肿瘤组织中Vimentin、CEA、ER、PR和p16阳性表达率分别为14.3%、90.5%、23.8%、42.9%和81.0%。经2检验,Vimentin(2=25.50)、CEA(2=20.50)、ER(2=27.29)、PR(2=10.17)和p16(2=22.17)在子宫内膜样腺癌和宫颈腺癌患者肿瘤组织中阳性表达率的差异均有统计学意义(P<0.05)。结论免疫组化法检测Vimentin、CEA、ER、PR和p16的表达有助于临床鉴别诊断宫颈腺癌和子宫内膜样腺癌。     

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目的 观察甲酰四氢叶酸钙(CF)联合5-氟尿嘧啶(5-Fu)治疗晚期乳腺癌的疗效和安全性.方法 选择既往经过蒽环类、紫杉类等药物治疗无效的晚期乳腺癌31例,中位年龄48.0岁(27～66岁).采用CF联合5-Fu化疗方案治疗.CF[150 mg/(m2·d)]+ 5-Fu[600 mg/(m2·d)],连用5天,每天静脉滴注不少于12h,每4周为一周期.观察有效率及不良反应.结果 完全缓解2例(6.5％),部分缓解7例(22.6％),病情稳定6例(19.4％),进展16例(51.6％).总有效率为29.0％,临床获益率为48.4％,其中激素受体阴性患者更能获益(P＜0.05).中位有效期为2.3月(95％CI:1.1～4.1),中位生存期为9.5月(95％CI:4.7～14.8).15例(48.4％)生活质量改善,6例(19.4％)稳定,10例(32.3％)下降.不良反应主要是胃肠道反应(11例)、骨髓抑制(4例)和口腔炎(9例).结论 CF+ 5-Fu联合静脉滴注二线治疗晚期乳腺癌疗效确切,不良反应可控,患者易于耐受,可以作为复发转移的晚期难治性乳腺癌的解救治疗.     

Expression of steroid hormone receptors and its prognostic significance in urothelial carcinoma of the upper urinary tract

To assess the expression status of steroid hormone receptors in upper urinary tract urothelial carcinoma (UUTUC), we immunohistochemically stained for androgen receptor (AR), estrogen receptor-α (ERα), ERβ, glucocorticoid receptor (GR), and progesterone receptor (PR) in 99 UUTUC specimens and paired non-neoplastic urothelial tissues. AR/ERα/ERβ/GR/PR was positive in 20%/18%/62%/63%/16% of tumors, which was significantly lower (except PR) than in benign urothelial tissues [57% (P < 0.001)/40% (P = 0.001)/85% (P = 0.001)/84% (P = 0.002)/13% (P = 0.489)]. There were no significant associations between each receptor expression pattern and histopathological characteristic of the tumors including tumor grade/stage. Kaplan-Meier and log-rank tests revealed no significant prognostic value of each receptor expression in these 99 patients. However, patients with UUTUC positive for either ERα or PR had a significantly higher risk of disease-specific mortality (P = 0.025), compared with those with UUTUC negative for both. PR positivity alone in pT3 or pT4 tumors was also strongly associated with the risk of disease-specific mortality (P = 0.040). Multivariate analysis further identified the expression of ERα and/or PR as a strong predictor for disease-specific mortality in the entire cohort of the patients (hazard ratio, 2.434; P = 0.037). Thus, in accordance with previous observations in bladder specimens, significant decreases in the expression of AR/ERα/ERβ/GR in UUTUC, compared with that in non-neoplastic urothelium, were observed. Meanwhile, the negativity of both ERα and PR in UUTUC as well as the negativity of PR alone in deeply invasive tumor was suggested to serve as a prognosticator.