涎腺腺样囊性癌中Cyclin D1、MMP-7和PRB2/p130表达及意义

目的探讨Cyclin D1、MMP-7和PRB2/p130蛋白在涎腺腺样囊性癌组织中的表达及与涎腺腺样囊性癌生物学行为的关系。方法应用免疫组化SP法检测46例涎腺腺样囊性癌和30例正常涎腺组织中Cyclin D1、MMP-7和PRB2/p130蛋白的表达。结果 Cyclin D1、MMP-7和PRB2/p130在涎腺腺样囊性癌中的阳性率分别为71.74%、67.39%、63.04%;Cyclin D1和PRB2/p130蛋白在涎腺腺样囊性癌中的表达与病理类型有关(P<0.05),MMP-7在涎腺腺样囊性癌中的表达与病理类型无关(P>0.05);Cyclin D1、MMP-7和PRB2/p130蛋白在涎腺腺样囊性癌复发组中的阳性率与无复发组相比,差异有显著性(P<0.05);Cyclin D1与PRB2/p130在涎腺腺样囊性癌中的表达呈负相关,与MMP-7表达呈正相关。结论 Cyclin D1、MMP-7和PRB2/p130蛋白的异常表达在涎腺腺样囊性癌发生、发展和复发中起重要作用,联合检测多个指标可能对患者预后的判断有指导意义。     

涎腺癌分子病理研究及临床应用进展

涎腺癌是一组异质性恶性肿瘤。世界卫生组织（2017）头颈部肿瘤分类将涎腺癌分为22种组织病理学亚型,临床最常见亚型包括黏液表皮样癌、腺样囊性癌、涎腺导管癌、腺泡细胞癌和分泌性癌等。涎腺癌各亚型组织形态学重叠,诊断和鉴别诊断困难。涎腺癌的主要治疗方式是手术切除,酌情术后放射治疗。对于局部进展、复发和转移性病例,治疗方式有...     

Tenascin-C和CD9在涎腺肿瘤中的表达

目的:探讨Tenascin-C(Tn-C)和CD9在涎腺肿瘤中的表达及其在涎腺肿瘤中鉴别诊断的价值.方法:应用免疫组织化学SP显色法检测Tn-C、CD9在多形性腺瘤(PA)、腺样囊性癌(ACC)、黏液表皮样癌(MEC)和腺泡细胞癌(ACCa)中的表达.结果:Tn-C、CD9在4种涎腺肿瘤中均有表达,Tn-C在多形性腺瘤...     

肺黏液表皮样癌的分子特征

目的:探讨肺黏液表皮样癌的分子特征.方法:回顾性对2013年7月至2016年12月13例病理确诊并接受治疗的肺黏液表皮样癌临床特征和分子特点进行分析.结果:EGFR基因突变率为15.38%(2/13),且2例均为L861Q点突变,EGFR基因状态与性别(P=1.000)、年龄(P=1.000)、吸烟史(P=0.848)及分期(P=1.000)均无相关性;MAML2融合基因阳性率为45.45%(5/11),MAML2融合基因状态与性别(P=0.521)、年龄(P=0.521)、吸烟史(P=1.000)及分期(P=0.924)均无相关性(P>0.05).结论:肺黏液表皮样癌中EGFR基因最常见的突变为L861Q,EGFR基因野生型患者中存在MALM2基因融合.     

结直肠癌组织中EGFR及HER-2的表达及临床意义

目的：探讨结直肠癌组织中表皮生长因子受体（ epiderma1 growth factor receptor,EGFR）和人类表皮生长因子受体-2（ hu-man epiderma1 receptor-2,HER-2）蛋白的表达,并分析二者与临床病理特征的关系。方法采用免疫组化PV-9000两步法检测78例结直肠癌组织中EGFR和HER-2的表达,分析二者表达与结直肠癌临床病理特征的关系;应用银染原位杂交（ si1ver in situ hybridization,SISH）法检测结直肠癌组织中HER-2基因扩增情况。结果 EGFR在结直肠癌组织中的阳性率为69.23%（54/78）,EGFR表达与结直肠癌浸润深度、淋巴结转移呈正相关,与患者性别、年龄、肿瘤大小、细胞分化程度、Dukes分期无关;HER-2在结直肠癌组织中的阳性率为25.64%（20/78）,HER-2表达与结直肠癌浸润深度、淋巴结转移呈正相关,与患者性别、年龄、肿瘤大小、细胞分化程度、Dukes分期无关。EGFR与HER-2蛋白表达呈正相关。20例HER-2蛋白阳性者中,10例HER-2基因扩增;其中15例HER-2蛋白（~）中有10例HER-2基因扩增,占高表达组的66.67%;5例HER-2蛋白（+）者无HER-2基因扩增。结论 EGFR和HER-2蛋白在结直肠癌中均呈高表达,EGFR和HER-2的表达与结直肠癌侵袭、转移密切相关,二者可能存在协同作用。HER-2蛋白（~）与HER-2基因扩增密切相关,故该类患者可考虑先行免疫组化初步筛选,再行SISH法检测确认,从而为结直肠癌分子的靶向治疗提供有价值的信息。     

卵巢黏液性肿瘤中EGFR表达和K-RAS基因的突变

目的 研究卵巢黏液性肿瘤中表皮生长因子受体(epidermal growth factor receptor,EGFR)蛋白的表达及K-RAS基因的突变,探讨卵巢黏液性肿瘤的发病机制及靶基因治疗的可行性.方法 应用免疫组化PV 9000两步法和PCR-RFLP法分别检测20例卵巢黏液性囊腺瘤、40例卵巢黏液性交界性囊腺瘤和40例卵巢黏液性囊腺癌中EGFR蛋白的表达和K-RAS基因的突变情况.结果 EGFR在卵巢黏液性囊腺瘤、黏液性交界性囊腺瘤和囊腺癌中的阳性表达率分别为0、37.5%、67.5%(P<0.01).K-RAS在卵巢黏液性囊腺瘤、黏液性交界性囊腺瘤和囊腺癌中的突变率分别为0、37.5%、7.5%,交界组突变率明显高于其他2组,但卵巢囊腺瘤与囊腺癌比较,差异无统计学意义(P>0.05).EGFR与卵巢黏液性囊腺癌的临床分期、病理分级、患者年龄无关(P<0.05),与肿瘤的大小相关(P<0.05).EGFR与卵巢黏液性交界性肿瘤临床病理分期、肿瘤大小、患者年龄无关(P>0.05).K-RAS基因突变与卵巢黏液性交界性肿瘤临床病理分期、肿瘤大小无关(P>0.05),与患者年龄相关(P<0.05).EGFR的表达和K-RAS基因的突变在卵巢黏液性交界性肿瘤中无相关性(P>0.05).结论 EGFR对卵巢黏液性交界性囊腺瘤和卵巢黏液性囊腺癌的形成起到了一定的作用,而K-RAS基因则可能是卵巢黏液性交界性囊腺瘤形成的一个重要因素.     

HER-2/neu基因在涎腺肿瘤中的扩增及表达

一、材料和方法1 材料　收集湖南医科大学 1 991年 1 2月～ 1 997年 4月存档蜡块中涎腺肿瘤 37例 ,其中粘液表皮样癌 2 0例、腺样囊性癌 1 1例、腺泡细胞癌 4例、恶性混合瘤 2例。从上述蜡块中随机选取粘液表皮样癌 5例、腺样囊性癌 4例、腺泡细胞癌 2例、恶性混合瘤 1例 ,以及癌旁正常组织 1例 ,以便行荧光原位杂交法 (ＦＩＳＨ)检测。2 方法　标本经 4%甲醛固定、石蜡包埋、切片。采用链霉素抗生物素蛋白 过氧化酶免疫组织化学染色方法检测ＨＥＲ 2 /ｎｅｕ蛋白的表达 ,ＤＡＢ显色。鼠抗人ＨＥＲ 2 /ｎｅｕＩｇＧ、生物素化兔抗鼠抗…     

腺样囊性癌组织中CD43的表达及临床意义

目的 探讨腺样囊性癌(adenoid cystic carcinoma, ACC)中CD43的表达，比较其在ACC不同组织学亚型、涎腺ACC与非涎腺ACC之间的表达差异，分析ACC中CD43与CD117表达的相关性及临床意义。方法 选取2011～2019年皖南医学院弋矶山医院病理科ACC 96例和对照组103例(包括上皮-肌上皮癌18例、多形性腺瘤20例、黏液表皮样癌20例、Warthin瘤22例及基底细胞腺瘤23例),采用免疫组化EnVision两步法检测CD43和CD117蛋白表达，并分析CD43表达与ACC临床病理特征的关系。结果 96例ACC中，74例CD43蛋白阳性(阳性率为77.1%),对照组CD43阳性率为3.9%;筛状型ACC 70例、管状型ACC 19例、实体型ACC 18例，其中筛状型ACC中CD43蛋白阳性57例(阳性率为81.4%),管状型ACC中CD43蛋白阳性16例(阳性率为84.2%),两者差异无统计学意义，而实体型ACC中CD43蛋白阳性仅9例(阳性率为50%),CD43蛋白阳性率较前两种分型显著降低；非涎腺ACC中CD43蛋白阳性率为22.2%(2/9...     

涎腺腺样囊性癌组织中HPV感染及p53、p16、EGFR、Cdc2蛋白表达与预后的关系

目的初步探讨HPV感染及p53、p16、EGFR及Cdc2表达与涎腺腺样囊性癌(adenoid cystic carcinoma,ACC)预后的关系。方法收集76例涎腺ACC手术标本,分别采用PCR-DNA反向点杂交及免疫组化SP法检测肿瘤组织中HPV-DNA及p53、p16、EGFR及Cdc2表达,收集临床资料并随访。Kaplan-Meier模型分析患者生存情况,Log-rank检验比较生存曲线,多因素Cox回归模型进行预后分析。结果涎腺ACC组织中HPV感染率为0(0/76)。p53、p16、EGFR及Cdc2蛋白在肿瘤组织中的阳性率分别为76.3%(58/76)、57.9%(44/76)、60.5%(46/76)及64.5%(49/76)。p53、p16、EGFR及Cdc2蛋白表达与患者性别、年龄、肿瘤部位、TNM分期及病理类型无关(P均0.05)。EGFR阳性患者中位总生存期(overall survival,OS)低于阴性患者(χ~2=19.111,P0.01)。EGFR阳性患者中位无进展生存期(progression-free survival,PFS)低于阴性患者(χ~2=6.621,P0.01)。Cdc2阳性患者中位OS短于阴性患者(χ~2=3.870,P0.05)。Cdc2阳性患者中位PFS低于阴性患者(χ~2=6.755,P0.01)。多因素Cox回归模型分析显示EGFR、Cdc2蛋白表达(RR=13.417、13.075,P均0.001)是涎腺ACC患者预后的独立危险因素。结论涎腺ACC组织中未检测出HPV感染。p53、p16、EGFR及Cdc2蛋白在涎腺ACC组织中呈不同程度表达,p16不能作为涎腺ACC患者HPV感染状态的替代指标。EGFR及Cdc2阳性表达是涎腺ACC患者预后的独立危险因素,临床对EGFR及Cdc2蛋白表达患者应密切随访。     

276例手术切除肺腺癌亚型与EGFR/ALK基因状态

目的:探讨手术切除肺腺癌各亚型EGFR和ALK基因状态分布.方法:应用ARMS方法检测手术切除肺腺癌石蜡组织中EGFR基因突变和ALK融合基因情况.结果:276例肺腺癌手术样本中,EGFR基因突变率为54.71％(151/276),其中19del为28.99％(80/276),L858R为23.19％(64/276),20-ins为0.72％(2/276),L861Q为0.72％(2/276),G719X为1.09％(3/276),S768I为0.36％(1/276)和T790M为0.72％(2/276),其中包含G719X+S768I,19del+T790M,L858R+T790M各1例,ALK基因融合阳性率为5.80％(12/207),在肺腺癌各亚型中EGFR基因突变附壁状腺癌,腺泡状腺癌,乳头状腺癌,实体状腺癌和浸润性黏液腺癌之间差异有统计学意义(P＜0.001,P=0.009,P=0.023,P＜0.001和P=0.030),与其他类型之间差异均无统计学意义(P＞0.05);在肺腺癌各亚型中ALK融合基因突变各亚型之间差异均无统计学意义(P＞0.05).结论:肺腺癌组织学亚型与EGFR基因突变有关,附壁状腺癌、腺泡状腺癌和乳头状腺癌出现EGFR基因突变比其他亚型更加明显.     

表皮生长因子受体与他莫西芬耐药机制

雌激素受体及其信号通路在乳腺癌的发生发展中发挥着关键作用.到目前为止,抑制或阻断雌激素信号通路的内分泌治疗尤其是他莫西芬,仍是对雌激素受体阳性乳腺癌患者最有效的治疗手段之一.然而,他莫西芬的耐药问题直接影响了乳腺癌患者的治疗及预后.最近多项研究表明雌激素受体与表皮生长因子受体家族尤其是HER2介导的信号传导通路在多个点上相互交叉,彼此影响,与他莫西芬的耐药密切相关     

Transforming growth factor alpha and epidermal growth factor in human pancreatic cancer.

Overexpression of the epidermal growth factor receptor (EGFR) has been reported as an important molecular abnormality in human pancreatic cancer. There is in vitro evidence that simultaneous overproduction of one of its ligands, transforming growth factor alpha (TGF-alpha), might result in an autocrine loop with an increased proliferation signal. We analysed by immunocytochemical staining a retrospective series of human pancreatic cancers, chronic pancreatitis, and normal fetal and adult pancreatic tissues for the presence of TGF-alpha and epidermal growth factor (EGF). Ductal epithelial cells showed TGF-alpha immunoreactivity in both normal tissue and chronic pancreatitis, and 95 per cent of tumours showed strong immunoreactivity. In contrast, EGF immunoreactivity was not found in normal pancreas, but was expressed in 12 per cent of pancreatic carcinomas. Well-defined areas of EGF immunoreactivity in exocrine ducts showing reactive changes in pancreatitis might represent a benign response to tissue damage similar to that previously described in the gastric mucosa.     

Dependence of activation of the epidermal growth factor receptor on its affinity and oligomerization

R. E. Kavetskii Institute for Problems in Oncology and Radiobiology, Academy of Sciences of the Ukrainian SSR, Kiev. (Presented by Academician of the Academy of Medical Sciences of the USSR A. S. Efimov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 113, No. 1, pp. 84–87, January, 1992.     

表皮生长因子对骨髓间充质干细胞体外趋化的影响

目的观察表皮生长因子(EGF)对骨髓间充质干细胞(BMSCs)的体外趋化的影响,探讨EGF对BMSCs迁移影响的可能机制。方法密度梯度离心法分离BMSCs,体外培养、传代纯化。利用Transwell小室建立体外趋化迁移模型。分别观察0,25,50,75,150ng/ml浓度的EGF对BMSCs的体外趋化作用,以及加入EGF中和抗体后对BMSCs趋化作用的影响;应用反转录聚合酶链反应(RT-PCR)方法检测大鼠BMSCs有无表皮生长因子受体(EGFR)的表达。结果细胞迁移实验结果:EGF以浓度梯度(0,25,50,75,150ng/ml)依赖方式促进大鼠BMSCs的定向迁移,作用显著(P<0.05)。抗体中和后的迁移实验:75ng/ml的EGF对BMSCs的趋化作用可被EGF中和抗体明显减弱(P<0.01)。RT-PCR证实BMSCs表达EGFR。结论在体外,EGF以浓度依赖方式引起BMSCs的定向迁移,BMSCs表达EGF的受体EGFR。     

表皮生长因子受体介导的新型肝癌靶向性基因转移

如何使得外源基因稳定地从吞噬溶酶体中释放 ,是提高受体介导基因转移系统转移效率的关键。本文以绿色荧光蛋白质粒为报告基因 ,合成针对表皮生长因子受体 (EGFR)的相应 16肽配体寡肽和流感病毒血凝素HA2 0寡肽 ,并与多聚赖氨酸连接 ,连接物与绿色荧光蛋白报告基因按 1∶1混合 ,构建新型肝癌靶向性转移系统 ,命名为四元复合体。分别以四元复合体和脂质体在体内外进行基因转染 ,流式细胞仪和激光共聚焦显微镜检测绿色荧光蛋白表达。结果表明 ,四元复合体介导基因定向转染至肿瘤细胞 ,其转染率为 44 95 % ,显著高于脂质体转染组( 3 3 0 9% ,P <0 0 5 ) ,动物实验证明 ,四元复合体介导绿色荧光蛋白特异性表达于肿瘤细胞 ,具有良好的应用前景     

Immunohistochemical investigation of epidermal growth factor receptor expression in ameloblastomas

Immunohistochemical analysis was performed to determine the localization of epidermal growth factor receptor (EGFR) in ameloblastomas. Ameloblastoma samples were classified into follicular, plexiform, and basal cell types. The number of cases in each category was 17, 19 and 3, respectively. Ameloblastomas, disregarding their histological type, consist of two cell forms: peripheral columnar cells and central stellate cells. The frequency of EGFR expression was much higher in the latter than in the former (P<0.005). On analysis with respect to histological types, the frequency of EGFR expression in columnar cells was not significantly different between the follicular and the plexiform types, but was observed more frequently in the stellate cells in the follicular than in the plexiform ameloblastomas (P<0.05). This pattern of EGFR expression was not consistent with the PCNA staining pattern, but was similar to that of keratin expression which we have reported previously. The present study suggests that EGFR expression in ameloblastomas is closely associated with tumour differentiation, and squamous differentiation in particular.     

Allelic length of a CA dinucleotide repeat in the egfr gene correlates with the frequency of amplifications of this sequence--first results of an inter-ethnic breast cancer study

Overexpression of the epidermal growth factor receptor (EGFR) is a common finding in invasive breast cancer and represents a potential target for new treatment options. However, little is known about the parameters that might indicate a potential clinical response for these anti-EGFR-based therapies. In order to gain further insights into the interplay between the length of a CA-SSR I repeat in intron 1 of egfr, copy numbers of this untranslated regulatory sequence, and protein expression, the present study investigated breast cancers from Germans and Japanese patients by microsatellite analysis, quantitative 5' nuclease assay by egfr enzyme-linked immunosorbent assay (ELISA), and comparative genomic hybridization (CGH). Japanese breast cancer patients displayed significantly longer alleles for the CA-SSR I repeat (p < 0.001), associated with significantly lower EGFR expression (mean 65 versus 36 fmol/mg membrane protein). Allelic imbalance (restricted to CA-SSR I) was observed in 55% of the informative Japanese breast cancers compared with only 34% of the German breast cancer reference group. Using a quantitative 5' nuclease assay for egfr, a significantly higher percentage of Japanese breast cancer patients revealed amplifications of the CA-SSR I repeat (p < 0.01). Japanese patients with these amplifications were characterized by a significantly higher EGFR content compared with the German breast cancer patients (p < 0.05). These data show, on the one hand, that the correlation of EGFR overexpression and an inherited CA repeat polymorphism within intron 1 of egfr is a general finding in breast cancer, as has been shown previously. On the other hand, the data demonstrate clearly for the first time an interaction between the length of a polymorphism in intron 1 of egfr as an inherited genetic factor and the frequency of egfr amplification, as an acquired genetic factor, both factors contributing to EGFR overexpression in breast cancer. This new knowledge about mechanisms of regulation of EGFR expression might serve as an additional basis for evaluating anti-EGFR-based therapies.     

Disappearance of epidermal growth factor receptor is essential in the fusion of the nasal epithelium

Epidermal growth factor (EGF) and receptor (-R) signaling pathway is required for epithelial cell growth and differentiation such as the degeneration of the medial edge epithelial cells during the fusion process of secondary palate formation. As epithelial fusion takes place during primary palate formation, we investigated the involvement of the EGF-R in fusion of the medial (MNP) and lateral (LNP) nasal prominences of the mouse embryo was examined. Immunoreactivity of EGF-R was investigated in embryonic day 10 embryos (32–37 somite stages). The EGF-R immunoreactivity was observed in the nasal epithelia of the presumptive fusion area before fusion. It became undetectable just prior to the fusion and faintly reappeared at the time of the fusion. In contrast, the non-fusing epithelial cells of the nasal groove maintained the immunoreactivity throughout these stages. In order to elucidate whether the EGF/EGF-R signaling pathway was involved in nasal epithelial fusion, EGF solution was injected into the exocoelum of explanted mouse embryos, and the embryos were cultured for 18–24 h by whole embryo culture (WEC). This exogenous EGF inhibited fusion of nasal pro-minences in 66.7–81.5% of the embryos. Treatment with EGF for 4–14 h showed that exogenous EGF dis-turbed the EGF-R disappearance and normal alteration of epithelial cell morphology in the fusion area. These results suggest that temporal disappearance of the EGF/EGF-R signaling from presumptive fusion of the nasal prominences is required for morphological change of the epithelial cells leading to the fusion of MNP and LNP.     

Secretion of high amounts of hepatocyte growth factor is a characteristic feature of cancer‐associated fibroblasts with EGFR‐TKI resistance‐promoting phenotype: A study of 18 cases of cancer‐associated fibroblasts

Humoral factors from cancer‐associated fibroblasts (CAFs) reportedly affect epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI) resistance in cancer cells with EGFR mutations. The aim of this study was to identify the robust humoral factors secreted from CAFs that induce the primary resistance to EGFR‐TKI. We evaluated the EGFR‐TKI sensitivity of EGFR‐mutant lung adenocarcinoma cell line (PC‐9) treated with condition media (CM) from 18 cases of CAFs and matched non‐cancerous‐tissue‐associated fibroblasts (NCAFs). We measured the expression levels of hepatocyte growth factor (HGF), interleukin‐6, fibroblast growth factor‐2, insulin‐like growth factor‐1, and vascular endothelial growth factor‐A in CAFs and NCAFs. We examined whether HGF neutralizing antibody could annul the EGFR‐TKI resistance induced by CM from CAFs. Compared to CM from NCAFs, CM from CAFs increased the resistance of PC‐9 cells to EGFR‐TKI in five out of 18 cases. Relative expression ratio of HGF messenger RNA was significantly higher in these five CAFs compared to others (P = 0.0013), whereas other cytokines were not. In four of these five cases, the addition of HGF neutralizing antibody significantly decreased the survival ratio of PC‐9 cells. This study suggests that the secretion of higher amounts of HGF is the robust feature of EGFR‐TKI resistance‐promoting CAFs.     

EGFR mutations in non-small-cell lung cancer among smokers and non-smokers: a meta-analysis

Mounting evidence has suggested somatic mutations in the EGFR gene are associated with better responsiveness to EGFR tyrosine kinase inhibitors (TKIs) in patients with non-small-cell lung cancer (NSCLC). Some, but not all, studies have reported that the mutations were more frequently observed in patients without a smoking history. To comprehensively address this issue, we performed a meta-analysis to evaluate the association between cigarette-smoking history and mutation of the EGFR gene in NSCLC. Twenty-six studies, involving 3,688 patients with NSCLC were included in the analysis. The pooled analysis shows that the incidence of EGFR mutations in NSCLC differs according to cigarette-smoking history. The odds ratio (OR) for the EGFR mutation in non-smokers relative to smokers was 4.829 (95% confidence interval [CI]: 3.598-6.482; P < 0.001). These data may assist clinicians in assessing the likelihood of EGFR mutations in patients with NSCLC when mutational analysis is not feasible.