RCAS1在宫颈癌组织中的表达及其与HPV16感染的关系

背景与目的:表达在SiSo细胞上的受体结合肿瘤抗原(receptor-binding cancer antigen expressed on SiSo cells,RCAS1)在多种肿瘤组织中呈高表达,并与肿瘤逃避免疫监视有关.本研究检测RCAS1蛋白在宫颈癌组织中的表达及其与HPV16感染的相关性,并探讨其临床意义.方法:采用免疫组化SP(streptavidin-peroxidase)法,分别检测71例宫颈癌、76例宫颈上皮内瘤样病变(CIN)及20例正常宫颈上皮组织中RCAS1蛋白与HPV16 E7蛋白的表达,并分析两者的表达与临床病理因素的关系.结果:宫颈癌组织中,RCAS1蛋白主要表达于癌细胞膜和/或细胞浆,HPV16 E7蛋白主要表达于癌细胞核.正常宫颈上皮组织不表达RCAS1蛋白,CIN与宫颈癌组织中RCAS1蛋白的表达率分别为39.47%和77.46%,HPV16 E7蛋白的表达率分别为0.05%、28.94%和61.97%,提示随着宫颈病变恶性程度的进展,RCAS1与HPV16 E7表达均逐渐增强(P＜0.05).低分化宫颈癌组中RCAS1表达显著高于高、中分化宫颈癌组(P=0.002),但与患者年龄、临床分期及组织学分型无关(P＞0.05);HPV16 E7在鳞癌组中的表达显著高于腺癌组(P=0.000),但与患者年龄、临床分期、组织学分级无关(P＞0.05).RCAS1的表达与HPV16感染在宫颈癌中的表达呈正相关(r=0.780,P=0.000).结论:RCAS1基因在宫颈癌组织中表达增强,RCAS1表达强度与宫颈癌恶性程度相关;RCAS1阳性的宫颈癌组织中存在HPV16感染.     

阴茎癌组织中热休克蛋白70表达与人乳头瘤病毒感染的关系

目的探讨热休克蛋白70(HSP70)表达与人乳头瘤病毒(HPV)感染的关系. 方法用免疫组化和原位PCR技术对78例阴茎癌组织进行检测.结果阴茎癌组织中HSP70阳性表达率为 61.5%(48/78),明显高于对照组的11.5%(P＜0.01),而与癌旁非典型增生组织中的表达无明显差异( P＞0.05).阴茎癌组织中HPV DNA阳性率为 69.2%(54/78), 54例HPV DNA阳性组织中有38例(70.4%)HSP70表达阳性,高于HPV DNA阴性组织的表达率(41.7%,P＜0.05). 结论 HSP70与阴茎癌的发生发展有密切关系,HSP70的表达增高可能与HPV16和18的感染有关.     

EGF及EGFR在胃癌及癌前组织中的表达和意义

作者采用免疫组化ＬＳＡＢ法对８２例正常胃粘膜、胃癌前病变及胃癌组织进行ＥＧＦ和ＥＧＦＲ的检测。结果：ＥＧＦ及ＥＧＦＲ在正常胃粘膜无表达；在癌前组织中阳性率分别为８．３％和４１．７％；在胃癌中表达率分别为３５．５％和４５．２％。ＥＧＦ及ＥＧＦＲ的表达与胃癌的分化程度、浸润及淋巴结转移有关；ＥＧＦ和ＥＧＦＲ在胃癌中的表达存在相关性。结果表明，ＥＧＦ－ＥＧＦＲ系统在胃癌的发生、发展中起着一定作用，两者可作为反映胃癌生物学行为的指标。     

扁桃体鳞癌中HPV感染与EGFR、VEGF表达的相关性研究

目的:研究扁桃体鳞癌(squamous cell carcinomas of the tonsil tonsillar,SCCs)中人乳头瘤病毒(human papillomavirus,HPV)感染与血管内皮生长因子(vascular endothelial growth factor,VEGF)和表皮生长因子受体(epidermal growth factor,EGFR)表达的关系,探讨HPV与EGFR和VEGF在扁桃体鳞癌发生中的交互效应。方法:采用多重实时荧光定量聚合酶链反应(multiplex real-time polymerase chain reaction,MT-PCR)检测85例扁桃体鳞癌HPV DNA及型别,通过HPV DNA分析进行HPV感染状况的测定;同时采用半定量免疫组化检测HPV(+)组和HPV(-)组中VEGF、EGFR蛋白表达情况。结果:扁桃体鳞癌中HPV感染率为49.4%(42/85),HPV-16型占所有感染者的比例为90.5%(38/42),明显高于其他型别;HPV(+)组EGFR蛋白表达明显低于HPV(-)组(P值均<0.01);HPV(+)组与HPV(-)组VEGF蛋白表达无明显差异;此外,VEGF表达与EGFR、患者的年龄、性别、TNM分期、组织学分级均无明显相关性。结论:HPV感染与扁桃体鳞癌的发生存在相关性,HPV相关的扁桃体鳞癌中,HPV基因可能通过改变EGFR表达致癌,为HPV致癌机理进一步研究提供一个新的视角,具有重要的理论意义。     

EGF mRNA和EGFR mRNA在肝细胞癌组织中的表达及其意义

背景和目的有众多证据表明表皮生长因子受体(epidermalgrowthfactorreceptor,EGFR)家族在一系列恶性肿瘤的发生发展中起重要作用,但EGFR与肝癌的关系目前尚未明确。本文旨在探讨表皮生长因子(epidermalgrowthfactor,EGF)及其受体的mRNA在人肝细胞癌(hepatocellularcarcinoma,HCC)组织中的表达及其意义。方法用逆转录聚合酶链反应(RT-PCR)技术检测60例HCC患者癌组织及癌旁肝组织中EGFmRNA和EGFRmRNA的表达情况。结果EGFmRNA阳性率在肝癌组织中(60%,36/60)显著低于癌旁组织(80%,48/60)(P<0.05);EGFRmRNA阳性率在肝癌组织中(60%,36/60)显著高于癌旁组织(41.67%,25/60)(P<0.05)。EGFRmRNA在肝癌组织中的检出率与临床分期、门静脉癌栓、肝外转移、术后复发、肿瘤数目等明显有关,而与肿瘤直径、血清AFP水平、分化程度以及癌旁肝硬化无明显关系。EGFmRNA检出率与肿瘤直径明显有关,而与临床分期、门静脉癌栓、肝外转移、术后复发、肿瘤数目、血清AFP水平、分化程度以及癌旁肝硬化等无明显关系。结论本研究结果提示EGF可能与肝癌的发生、发展无关;而EGFR与肝癌的发生、发展及术后复发有关;可作为预测肝癌复发、转移的参考指标。     

乳腺浸润性导管癌组织中 HPV18 DNA 及 p53 蛋白的表达

目的：探讨人乳腺浸润性导管癌组织中HPV18DNA和p53蛋白的表达及二者间的关系。方法：采用分子原位杂交和免疫组化技术检测60例乳腺浸润性导管癌、30例乳腺腺病和30例正常乳腺组织中HPV18DNA和p53蛋白。结果：癌组中HPV18DNA阳性和HPV18DNA阴性两组间p53蛋白的阳性表达均有显著性差异（P〈0．03），HPV18DNA阳性组与p53蛋白阳性表达呈显著负相关（r=-0．2954、P〈0．04）。结论：HPV18感染后导致野生型p53的灭活和降解可能涉及HPV18感染后人乳腺上皮细胞癌变的转化过程。     

乳腺浸润性导管癌组织中HPV16DNA与p53蛋白表达的研究

 目的 检测人乳腺浸润性导管癌组织中HPV16DNA和p53蛋白，探讨HPV16型感染和p53蛋白表达与人乳腺癌之间的关系。方法 采用分子原位杂交和免疫组化技术检测和分析50例乳腺浸润性导管癌、30例正常乳腺组织中HPV16DNA和p53蛋白二者之间的表达关系。结果 癌组中HPV16DNA阳性和HPV16DNA阴性两组阃p53蛋白的表达均有显著性差异（P〈0．01），HPV16DNA阳性组显示与p53蛋白表达呈负相关（P〈0．02）。结论 HPV16感染后导致野生型p53的降解可能涉及HPV16感染后人乳腺上皮细胞癌变的病理发生过程。     

肿瘤组织中人乳头瘤病毒HPV基因组相关序列的检测

本文报道应用核酸分子杂交方法,以[α-(32)P]-dTTP标记的HPV16型基因组为探针,共检测恶性肿瘤53例(标本包括宫颈癌22例,阴茎癌3例、膀胱癌6例、肾癌3例、肺癌7例、胃癌1例、结肠癌11例)、7例良性肿瘤、8例正常上皮组织中HPV基因组相关序列。检测结果表明,在恶性肿瘤中仅于宫颈癌组织检测出HPV16型基因组相关序列59.1％,P<0.01。而良性肿瘤和正常上皮组织中均未检测出HPV16型和其他型别基因组相关序列。此种阴性结果,可能与地理分布、病变组织的病理类型、检测使用的探针和方法、例数少等因素有关。为进一步探讨HPV感染与肿瘤的关系,尚需深入研究。     

杆状病毒表达系统及其在HPV预防疫苗研究中的应用

杆状病毒表达系统被广泛用于表达外源基因,利用该系统表达的HPV衣壳蛋白可以自我组装成病毒样颗粒,是一种应用前景广阔的宫颈癌预防 疫苗。     

转化生长因子α及其受体在人脑星形细胞瘤中的表达及意义

目的　研究转化生长因子α(transforminggrowthfactoralpha ,TGF α)及其表皮生长因子受体 (epidermalgrowthfactorreceptor ,EGFR)在人脑星形细胞瘤中的表达及意义。方法　采用免疫组织化学方法检测 5 0例人脑星形细胞瘤标本和 10例正常人脑组织中TGF α和EGFR蛋白表达。结果　 5 0例人脑星形细胞瘤TGF α和EGFR蛋白表达总阳性率分别为 64 .0 % ( 3 2 /5 0 )和 68.0 % ( 3 4/5 0 ) ,正常脑组织未见阳性表达 (P <0 .0 1) ;二者密切相关 (P <0 .0 1) ,并与星形细胞瘤病理分级有显著相关性 ,其中Ⅰ～Ⅱ级者阳性率显著低于Ⅲ、Ⅳ级者 (P <0 .0 5 ) ;结论　TGF α和EGFR形成的自分泌环在人脑星形细胞瘤发生发展过程中起重要作用 ,同时检测它们可作为判断人脑星形细胞瘤临床分期、预后的重要指标     

Clinicopathological and prognostic significance of EGFR, VEGF, and HER2 expression in cholangiocarcinoma

Epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and human epidermal growth factor receptor 2 (HER2) have been considered as potential therapeutic targets in cholangiocarcinoma, but no studies have yet clarified the clinicopathological or prognostic significance of these molecules. Immunohistochemical expression of these molecules was assessed retrospectively in 236 cases of cholangiocarcinoma, as well as associations between the expression of these molecules and clinicopathological factors or clinical outcome. The proportions of positive cases for EGFR, VEGF, and HER2 overexpression were 27.4, 53.8, and 0.9% in intrahepatic cholangiocarcinoma (IHCC), and 19.2, 59.2, and 8.5% in extrahepatic cholangiocarcinoma (EHCC), respectively. Clinicopathologically, EGFR overexpression was associated with macroscopic type (P=0.0120), lymph node metastasis (P=0.0006), tumour stage (P=0.0424), lymphatic vessel invasion (P=0.0371), and perineural invasion (P=0.0459) in EHCC, and VEGF overexpression with intrahepatic metastasis (P=0.0224) in IHCC. Multivariate analysis showed that EGFR expression was a significant prognostic factor (hazard ratio (HR), 2.67; 95% confidence interval (CI), 1.52-4.69; P=0.0006) and also a risk factor for tumour recurrence (HR, 1.89; 95% CI, 1.05-3.39, P=0.0335) in IHCC. These results suggest that EGFR expression is associated with tumour progression and VEGF expression may be involved in haematogenic metastasis in cholangiocarcinoma.     

胃癌组织EGFR和VEGF的表达及其意义

目的探讨胃癌组织EGFR和VEGF的表达及其与临床病理特征的关系。方法应用免疫组化方法检测正常胃黏膜和胃癌切除标本EGFR和VEGF的表达,并与临床病理参数进行比较分析。结果胃癌组织EGFR和VEGF阳性表达率分别为64.7%和58.8%;正常胃黏膜组织EGFR和VEGF阳性表达率分别为0%和10.0%,差异有统计学意义（P=0.000）;EGFR阳性表达与肿瘤分化程度、浸润深度、淋巴结转移、远处转移及临床TNM分期呈显著相关,VEGF阳性表达与肿瘤分化程度、浸润深度、淋巴结转移、远处转移、脉管内癌栓和临床TNM分期呈显著相关（P〈0.01和P〈0.05）。EGFR表达阳性者有69.7%同时伴有VEGF表达阳性,EGFR和VEGF双阳性表达者的根治切除率仅为30.4%,明显低于阴性表达者（P=0.000）。结论胃癌组织EGFR和VEGF表达上调与肿瘤分化程度、浸润深度、淋巴结转移、远处转移、脉管内癌栓和TNM分期有关,EGFR促进肿瘤血管生长可能通过上调VEGF表达,胃癌组织EGFR和VEGF表达可能成为从同期别病例中甄别靶向治疗获益病例的主要预后指标。     

EGFR与HER-2在不同分子类型乳腺癌中的表达及其相关性分析

目的：探讨EGFR和HER-2在不同分子类型乳腺癌组织中的表达及其相关性。方法：回顾性分析2015年1月—2020年3月在邯郸市中心医院行手术治疗的乳腺癌患者资料650例(其中浸润性导管癌600例,浸润性小叶癌50例)及乳腺纤维腺瘤30例,应用免疫组织化学(IHC)方法对手术切除标本进行EGFR和HER-2蛋白表达检测,采用χ²检验及Spearman相关分析对数据进行统计学分析。结果：EGFR在乳腺浸润性导管癌中表达阳性率为48.7%,显著高于浸润性小叶癌(24.0%)及纤维腺瘤(16.7%)(P<0.01)。HER-2在乳腺浸润性导管癌中表达阳性率为27.8%,显著高于浸润性小叶癌(8.0%)及纤维腺瘤(6.7%)(P=0.002)。乳腺浸润性导管癌与浸润性小叶癌中,EGFR阳性率与HER-2评分等级呈正相关(r=1.000,P<0.05),且EGFR阳性率与HER-2阳性表达呈正相关(r=1.000,P<0.05)。EGFR阳性率在HER-2过表达型与三阴型乳腺癌组织中显著高于Luminal A型和Luminal B型,且Luminal B中HER-2阳性显著高于HER-2阴性亚型(P<0.001)。结论：EGFR、HER-2阳性率在乳腺浸润性导管癌显著升高,且EGFR阳性率与HER-2的评分等级及阳性表达率均呈正相关,EGFR在HER-2过表达型与三阴型乳腺癌组织中显著升高,为进一步研究HER-2阳性乳腺癌及三阴型乳腺癌的靶向药物治疗提供线索及理论依据。     

人绒毛膜促性腺激素对小鼠睾丸间质细胞的表皮生长因子及其受体的影响

目的　探讨HCG 与EGF、EGFR 共同调节生精过程机制, 为HCG 及EGF的临床应用提供一定依据。方法　应用免疫组化、体视学、图像分析方法对切除颌下腺和给予HCG 前后的ICR系小鼠睾丸间质细胞的EGF、EGFR 变化进行观察比较。结果　颌下腺切除后, 小鼠睾丸EGF阳性间质细胞体密度不变, 而光密度下降; 睾丸EGFR 阳性间质细胞体密度、光密度下降;EGF及EGFR阳性间质细胞体积减小。切除颌下腺后给予HCG, EGF 及EGFR 阳性间质细胞体密度、光密度增高, 比表面减小, 体积增大; EGF 及EGFR 阳性间质细胞的细胞核体积增大。结论　间质细胞EGF合成减少及EGFR 表达减弱是切除颌下腺引起小鼠少精症的重要原因之一;HCG 能增强睾丸间质细胞EGF合成及EGFR 的表达     

Decreased expression of human papillomavirus E2 protein and transforming growth factor-beta1 in human cervical neoplasia as an early marker in carcinogenesis

BACKGROUND AND OBJECTIVES: Human papillomavirus (HPV) is thought to be one of the possible causative factors in cervical carcinogenesis, and cervical carcinoma cells are refractory to tumor transforming growth factor (TGF)-beta1. The purpose of this study is to investigate the possible cause-effect association between HPV and TGF-beta1 during cervical tumorigenesis. METHODS: We assessed the expression of HPV capsid proteins, HPV-16 E7, HPV-16 E2 (C and N terminals), TGF-beta1, and their receptors TGF-beta RI and RII by immunohistochemistry in 48 paraffin-embedded blocks of tumor tissue derived from patients of cervical neoplasia. RESULTS: Expression of TGF-beta1 decreased as tumor cells progressed from cervical intraepithelial neoplasia (CIN)1, CIN2, CIN3, to microinvasive carcinoma (P < 0.05). Levels of TGF-betaRI and TGFbeta-RII stayed the same in all cases. HPV was found in 89.6% of the studied sections, and cervical lesions without HPV infection expressed significantly less TGF-beta1 (P < 0.05). By comparing the expression pattern of TGF-beta1 and HPV in the neoplastic cells with that of normal cervical epithelium in each section, we found loss of HPV-16 E2 higher in CIN3 (15/24) than in CIN1 or CIN2 (3/7), and there is a significant trend that loss of HPV-16 E2 expression correlated with a >50% loss of TGF-beta1 at the lesion site (P < 0.05). CONCLUSIONS: Our result showed co-suppression of HPV and TGF-beta1 expression during progression of cervical squamous cell cancer. Using antibody against HPV-16 E2 may be an auxiliary tool for the investigation of cervical tumor progression.     

Oestrogen Receptor-Mediated Modulation of the EGFR/MAPK Pathway in Tamoxifen-Resistant MCF-7 Cells

Oestrogen receptor (ER) levels are usually maintained on acquisition of tamoxifen resistance in the clinic, however, tumour re-growth is associated with increased expression of epidermal growth factor receptor (EGFR) and activation of the mitogen activated protein kinase (MAPK) pathway. In the present study we have used the ER down-regulator fulvestrant ('Faslodex') to investigate the influence of the ER on growth of a tamoxifen-resistant (TAM-R) human breast cancer cell line. Expression levels of ER mRNA and protein were equivalent in parental wild-type MCF-7 (WT) and TAM-R cells. Fulvestrant eliminated ER protein expression and inhibited proliferation in both cell lines. The growth inhibitory effects of fulvestrant were associated with a decrease in basal EGFR, c-erbB2 and ERK1/2 activity in TAM-R but not WT cells. ER functionality as determined by oestrogen response element (ERE)-luciferase reporter activity and expression of PgR, pS2 and transforming growth factor alpha (TGF) was significantly reduced in TAM-R compared to WT cells and was further decreased by fulvestrant treatment in both cell lines. Epidermal growth factor (EGF) and TGF significantly increased EGFR/MAPK pathway activity in both cell lines. Ligand-induced EGFR/MAPK activation promoted TAM-R cell growth in both the absence and presence of fulvestrant, whereas no proliferative activity was observed under the same conditions in WT cells. These results suggest that the ER modulates EGFR/MAPK signalling efficiency in TAM-R cells possibly through the regulation of TGF availability. This effect may be overcome by the action of exogenous EGFR ligands, which strengthen EGFR/MAPK signalling activity to generate endocrine-insensitive cell growth.     

HPV integration begins in the tonsillar crypt and leads to the alteration of p16, EGFR and c-myc during tumor formation

The prevalence of human papillomavirus (HPV) infection is high in the oropharyngeal mucosal regions, of which the tonsil is the most commonly affected. There may be a link between HPV and the pathogenesis of tonsillar cancer (TC), because of common anatomical characteristics between cervical and tonsillar cancer. We aimed to clarify whether HPV directly affects the oncogenesis and biologic behavior of TC by making a comparison between infection prevalence, physical status and viral loading numbers, and clinicopathologic prognostic factors. To compare HPV-related molecules between TC and tonsillitis (CFT), p16, survivin, HIF-1alpha, skp-1, cyclin A, cyclin B1, c-myc and EGFR were investigated. We observed a significant difference in HPV prevalence between 52 TCs and 69 CFTs (73.1% vs. 11.6%), and most of the HPVs were type 16 (87.2%) and nonepisomal (94.1%). Most TCs associated with HPV arose from the tonsillar crypts, and tended to be inverted and poorly differentiated. Compared with HPV-negative TC, HPV-positive TC showed a strong association with p16 overexpression (p<0.0001), and an inverse association with EGFR amplification (p=0.0478). HPV-16 integration status was strongly associated with c-myc amplification (p=0.034) and HIF-1alpha overexpression (p=0.022). HPV-16 integration could be directly related to tonsillar carcinogenesis initially in tonsillar crypts, followed by cell cycle aberration such as p16 overexpression related to the G1-S phase.     

Combined analysis of HPV-DNA, p16 and EGFR expression to predict prognosis in oropharyngeal cancer

Molecular prognostic indicators for oropharyngeal squamous cell carcinoma (OSCC), including HPV-DNA detection, epidermal growth factor receptor (EGFR) and p16 expression, have been suggested in the literature, but none of these are currently used in clinical practice. To compare these predictors, 106 newly diagnosed OSCC for the presence of HPV-DNA and expression of p16 and EGFR were analyzed. The 5-year disease-free survival (DFS) and overall survival (OS) were calculated in relation to these markers and a multivariate Cox analysis was performed. Twenty-eight percent of the cases contained oncogenic HPV-DNA and 30% were positive for p16. The p16 expression was highly correlated with the presence of HPV-DNA (p < 0.001). Univariate analysis of the 5-year DFS revealed a significantly better outcome for patients with p16-positive tumors (84% vs. 49%, p = 0.009). EGFR-negative tumors showed a tendency toward a better prognosis in DFS (74% vs. 47%, p = 0.084) and OS (70% vs. 45%, p = 0.100). Remarkable and highly significant was the combination of p16 and EGFR expression status, leading to 5-year DFS of 93% for p16+/EGFR- tumors vs. 39% for p16-/EGFR+ tumors (p = 0.003) and to a 5-year OS of 79% vs. 38%, respectively (p = 0.010). In multivariate analysis p16 remained a highly significant prognostic marker for DFS (p = 0.030) showing a 7.5-fold increased risk for relapse in patients with p16-negative tumors. Our data indicate that p16 expression is the most reliable prognostic marker for OSCC and further might be a surrogate marker for HPV-positive OSCC. HPV+/p16+ tumors tended to have decreased EGFR expression, but using both immunohistological markers has significant prognostic implications.