子宫颈癌中Smad4和Runx3表达与HPV16感染的关系

目的探讨子宫颈病变组织中Smad4、Runx3蛋白表达和HPV16感染的关系。方法采用免疫组化SP法检测Smad4、Runx3在慢性子宫颈炎、子宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)和子宫颈鳞癌组织中的表达;PCR技术检测相应标本中HPV16感染情况。结果 Smad4在慢性子宫颈炎、CIN和子宫颈鳞癌组织中阳性率分别为80%(20/25)、69.8%(44/63)、40%(18/45),差异有显著性(P<0.01),Runx3在各组中阳性率分别为84%(21/25)、69.8%(44/63)、40%(18/45),差异有显著性(P<0.05)。在子宫颈鳞癌组织中,Smad4蛋白与肿瘤分化程度及有无淋巴结转移相关;Runx3蛋白表达下调与肿瘤分化程度、临床分期及有无淋巴结转移密切相关,表达差异均有显著性(P<0.05);Smad4、Runx3两者之间表达无相关性;HPV16与Smad4表达呈负相关(r=-0.327,P<0.05)。结论 Runx3蛋白表达下调,以及HPV16通过影响Smad4蛋白表达缺失,共同阻断TGF/Smads信号转导通路,促使子宫颈病变不断发展。     

子宫颈病变中HPV L1蛋白和p16的表达

目的 研究HPV L1蛋白和p16在子宫颈各种病变中的表达情况,探讨它们在子宫颈病变进展中的预测价值.方法 应用免疫组化方法检测41例各种子宫颈病变(CIN1级18例、CIN2级9例、CIN3级8例和浸润性鳞状细胞癌6例)中HPV L1蛋白和p16的表达.结果 HPV L1蛋白在各种子宫颈病变中的阳性率为26.8%.其中HPV L1在CIN1中的阳性表达率为38.9%,CIN2为44.4%,CIN3和浸润性鳞状细胞癌均无表达.p16在各种子宫颈病变中的阳性率为68.3%,其在CIN1中的阳性表达率为38.9%,CIN2为77.8%,CIN3和浸润性鳞状细胞癌均表达阳性.100%CIN3和浸润性鳞状细胞癌为p16+/HPV L1-,而61.1% CIN1中为p16-/HPV L1+或p16-/HPV L1-.结论 随着子宫颈病变的进展,HPV L1阳性表达率降低而p16阳性表达率增高.p16+/HPV L1-提示子宫颈鳞状上皮内瘤变有进展的可能,而p16-/HPV L1+和p16-/HPV L1-可能为无进展的或潜在消退的子宫颈病变.     

子宫颈癌中c-myc和hMLH1表达与HPV16感染的关系

目的探讨子宫颈病变中c-myc与hMLH1和HPV16表达的关系。方法应用免疫组化SP法检测c-myc与hM-LH1在慢性子宫颈炎、子宫颈上皮内瘤变(cervical intraepi-thelial neoplasia,CIN)和子宫颈癌患者中的表达水平;PCR技术检测相应标本中HPV16感染的情况。结果 c-myc在慢性子宫颈炎、CIN、子宫颈癌中的阳性率分别为26.7%(8/30))、50%(30/60)、69.2%(36/52),差异有统计学意义(P<0.05),hMLH1阳性率依次为66.7%(20/30)、56.7%(34/60)、30.7%(16/52),差异有统计学意义(P<0.05)。在子宫颈癌组织中,c-myc蛋白与肿瘤分化程度、临床分期以及有无淋巴结转移相关;hMLH1蛋白表达下调与子宫颈癌分化程度及是否有淋巴结转移密切相关,表达差异均有统计学意义(P<0.05);HPV16与c-myc蛋白表达呈正相关;与hM-LH1蛋白表达呈负相关。结论 HPV16可能是通过影响c-myc与hMLH1蛋白表达而在子宫颈癌的发生、发展中发挥作用。     

子宫颈腺癌中HPV16/18感染对p16Ink4a、Rb蛋白表达的影响

目的研究16、18型人乳头瘤病毒(HPV16/18)DNA与细胞周期相关蛋白p16Ink4a、Rb在子宫颈腺癌中的表达情况及HPV16/18感染对p16Ink4a、Rb蛋白表达的影响。方法采用组织微阵列技术结合原位杂交和免疫组化EliVision二步法标记检测HPV16/18DNA和p16Ink4a、Rb蛋白在86例子宫颈腺癌、15例子宫颈腺上皮异型增生及24例慢性子宫颈炎组织中的表达。结果子宫颈腺癌组和子宫颈腺上皮异型增生组HPV16/18DNA阳性表达率分别为65·1%和46·7%,均明显高于慢性子宫颈炎组8·3%(P<0·01);p16Ink4a蛋白在子宫颈腺癌组的阳性表达率为74·4%,显著高于慢性子宫颈炎组33·4%(P<0·01)。Rb蛋白在子宫颈腺癌组的阳性表达率为33·7%,低于慢性子宫颈炎组45·8%,但差异无显著性(P>0·05)。HPV16/18感染与子宫颈腺癌的病理分级和组织学类型无关,但与p16Ink4a蛋白表达呈正相关(P<0·05)。p16Ink4a与Rb蛋白表达与子宫颈腺癌的病理分级有关,G2、G3组p16Ink4a阳性表达率明显高于G1组(P<0·05),G3组Rb阳性表达率明显低于G1组(P<0·05)。p16Ink4a表达与子宫颈腺癌组织学类型有明显相关性,子宫内膜样腺癌p16Ink4a阳性表达率明显高于透明细胞腺癌(P<0·05)。结论子宫颈腺癌的发生与HPV16/18感染有关,HPV16/18感染可能影响p16Ink4a、Rb蛋白表达,使子宫颈腺上皮发生癌变并促进恶性发展。     

P16,Ki67与HPV16/18在宫颈病变中的表达及其临床意义

目的:研究多肿瘤抑制基因P16、细胞核增殖抗原Ki67及高危型人乳头状瘤病毒(high riskhuman papilloma virus,HPV16/18)在宫颈病变中的表达和临床意义。方法:采用免疫组织化学Elivision两步法检测P16和Ki67在宫颈非特异性炎症、宫颈上皮内瘤变(cervical intraepithelialneoplasia,CIN)I级、Ⅱ级和Ⅲ级及宫颈鳞状细胞癌中的表达,用原位杂交法检测HPV16/18的表达。结果:P16蛋白表达在非特异性炎症、CINⅠ级、Ⅱ级和Ⅲ级及宫颈癌中的阳性率分别为20.0%,55.6%,93.6%和100.0%;Ki67蛋白表达在非特异性炎症、CINⅠ级、Ⅱ级、Ⅲ级及宫颈癌中的阳性率分别为17.6%,61.1%,89.4%和100.0%,不同组别间两两比较差异均有统计学意义(P<0.05)。而且P16和Ki67的阳性表达率及染色强度呈递增趋势,表达存在分层现象。HPV16/18在非特异性炎症、CINⅠ级、Ⅱ级、Ⅲ级及宫颈癌中的阳性率分别为30.0%,61.1%,82.9%和100.0%,宫颈病变中HPV16/18的阳性率显著高于非特异性炎症组。结论:P16和Ki67蛋白检测作为宫颈病变的有效的生物学标记,可联合HPV16/18 DNA检测应用于宫颈癌及其癌前病变的筛查和诊断中。     

子宫颈病变组织中低分子量蛋白酶体表达与HPV16感染的关系

目的观察低分子量蛋白酶体(low molecular-weight protein,LMP)在子宫颈病变组织中的mRNA和蛋白表达,探讨其与HPV16感染的关系。方法以152例新疆维吾尔族妇女正常子宫颈上皮、子宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)和子宫颈鳞癌(cervical squamous cell carcinoma,CSCC)患者为研究对象,采用RT-PCR和免疫组化法鉴定LMP2和LMP7mRNA及蛋白表达水平;采用PCR技术检测相应标本HPV16感染情况。结果 (1)LMP2、LMP7随着子宫颈病变的加重其蛋白表达逐渐降低,且mRNA表达水平与蛋白表达趋势相一致。在CIN中LMP2、LMP7蛋白表达下调和缺失率分别为25.0%/15.6%、29.7%/23.4%;在子宫颈癌中LMP2、LMP7蛋白的表达下调和缺失率分别为17.5%/34.9%、23.8%/41.3%。临床病理参数进行分析发现LMP2、LMP7与子宫颈癌分化程度及淋巴结转移密切相关(P<0.05)。(2)PCR结果显示,HPV16的检出率随着子宫颈病变的进展而增加,在慢性子宫颈炎、CIN和子宫颈癌组织中阳性率分别为8%(2/25)、67.2%(43/64)和77.8%(49/63),且随着肿瘤恶性程度的增加其阳性表达率增加,各组间阳性表达差异有统计学意义(P<0.05)。在CIN中LMP7表达下调与HPV16感染有关(P<0.05),子宫颈癌中LMP2和LMP7表达下调与HPV16感染有关(P<0.05)。结论 LMP基因的转录表达下调或蛋白质表达缺失与维吾尔族妇女子宫颈癌病变进程密切相关,其中HPV16感染可能是重要原因之一。     

宫颈癌中α-enolase表达及其与HPV感染的关系

目的探讨烯醇化酶-α(α-enolase)蛋白在宫颈鳞癌中的表达及其与HPV感染的关系。方法应用免疫组化PV-9000两步法检测30例慢性宫颈炎、61例宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)和70例宫颈鳞癌组织中α-enolase蛋白的表达,同时应用基因芯片技术检测70例宫颈鳞癌中HPV感染情况。结果 (1)α-enolase蛋白表达于细胞质和(或)胞核中。在慢性宫颈炎、CIN和宫颈癌中,α-enolase蛋白在胞质表达的阳性率分别为4.17%(1/24)、18.5%(10/54)和54.3%(38/70),表达依次增强(P=0.000)。(2)宫颈癌中HPV总感染率为97.1%(68/70),共检出8种HPV基因型,分别为HPV16、18、58、31、52、59、66、68,构成比为80.0%、14.3%、4.3%、4.3%、2.9%、2.9%、1.43%、1.43%。双重感染10例,占14.3%。HPV16、18为主要致病基因型。(3)宫颈癌中α-enolase蛋白表达的定位与HPV16/18感染呈正相关(r=0.340,P=0.012)。结论宫颈鳞癌中α-enolase蛋白表达与HPV16/18感染密切相关,二者在宫颈鳞癌的发生过程中可能起着协同作用。     

Relationship between the expression of α-enolase in cervical carcinoma and HPV infection

目的 探讨烯醇化酶-α(α-enolase)蛋白在宫颈鳞癌中的表达及其与HPV感染的关系.方法 应用免疫组化PV-9000两步法检测30例慢性宫颈炎、61例宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)和70例宫颈鳞癌组织中α-enolase蛋白的表达,同时应用基因芯片技术检测70例宫颈鳞癌中HPV感染情况.结果 (1)α-enolase蛋白表达于细胞质和(或)胞核中.在慢性宫颈炎、CIN和宫颈癌中,α-enolase蛋白在胞质表达的阳性率分别为4.17%(1/24)、18.5%(10/54)和54.3%(38/70),表达依次增强(P=0.000).(2)宫颈癌中HPV总感染率为97.1%(68/70),共检出8种HPV基因型,分别为HPV16、18、58、31、52、59、66、68,构成比为80.0%、14.3%、4.3%、4.3%、2.9%、2.9%、1.43%、1.43%.双重感染10例,占14.3%.HPV16、18为主要致病基因型.(3)宫颈癌中α-enolase蛋白表达的定位与HPV16/18感染呈正相关(r=0.340,P=0.012).结论 宫颈鳞癌中α-enolase蛋白表达与HPV16/18感染密切相关,二者在宫颈鳞癌的发生过程中可能起着协同作用.     

Association of the expression of the low molecular-weight protein with HPV16 infection in cervical lesions

目的 观察低分子量蛋白酶体(low molecular-weight protein,LMP)在子宫颈病变组织中的mRNA和蛋白表达,探讨其与HPV16感染的关系.方法 以152例新疆维吾尔族妇女正常子宫颈上皮、子宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)和子宫颈鳞癌(cervical squamous cell carcinoma,CSCC)患者为研究对象,采用RT-PCR和免疫组化法鉴定LMP2和LMP7 mRNA及蛋白表达水平;采用PCR技术检测相应标本HPV16感染情况.结果 (1)LMP2、LMP7随着子宫颈病变的加重其蛋白表达逐渐降低,且mRNA表达水平与蛋白表达趋势相一致.在CIN中LMP2、LMP7蛋白表达下调和缺失率分别为25.0%/15.6%、29.7%/23.4%;在子宫颈癌中LMP2、LMP7蛋白的表达下调和缺失率分别为17.5%/34.9%、23.8%/41.3%.临床病理参数进行分析发现LMP2、LMP7与子宫颈癌分化程度及淋巴结转移密切相关(P<0.05).(2)PCR结果显示,HPV16的检出率随着子宫颈病变的进展而增加,在慢性子宫颈炎、CIN和子宫颈癌组织中阳性率分别为8%(2/25)、67.2%(43/64)和77.8%(49/63),且随着肿瘤恶性程度的增加其阳性表达率增加,各组间阳性表达差异有统计学意义(P<0.05).在CIN中LMP7表达下调与HPV16感染有关(P<0.05),子宫颈癌中LMP2和LMP7表达下调与HPV16感染有关(P<0.05).结论 LMP基因的转录表达下调或蛋白质表达缺失与维吾尔族妇女子宫颈癌病变进程密切相关,其中HPV16感染可能是重要原因之一.     

子宫颈鳞状细胞癌中MCM5和p16~(INK4A)的表达及其意义

目的探讨HPV 16感染的子宫颈癌中MCM5与p16~(INK4A)表达及其意义。方法采用RT-PCR及免疫组化SABC法检测HPV 16感染正常子宫颈、子宫颈上皮内病变(cervical intraepithelial neoplasia,CIN)包括CIN 1与CIN 2~3及子宫颈鳞状细胞癌中MCM5、p16~(INK4A)的mRNA及蛋白表达,并分析其临床意义。结果 MCM5、p16~(INK4A)mRNA在子宫颈癌组织中表达均明显高于正常组织(χ~2=-6.589,P0.001;χ~2=-4.349,P0.001);且随子宫颈病变程度的升高逐渐增加,差异有显著性(χ~2=57.141,P0.001;χ~2=47.628,P0.01);子宫颈癌中MCM5 mRNA的表达与临床分期、病理分级有关,Ⅰa~Ⅰb期明显低于Ⅱa~Ⅱb期(χ~2=-4.93,P0.01),其表达随病理分级降低而降低(χ~2=-4.017,P0.01);子宫颈癌中p16~(INK4A)mRNA表达随病理分级的降低而降低(χ~2=8.560,P0.01);MCM5、p16~(INK4A)mRNA在子宫颈鳞状细胞癌中表达最明显;MCM5和p16~(INK4A)蛋白表达呈正相关(r=0.497)。结论子宫颈癌中MCM5和p16~(INK4A)高表达,MCM5可较好的反应子宫颈的恶性增生,与p16~(INK4A)联合检测对完善CIN分级及预后的判断意义重大。     

Interleukin-16

Interleukin 16 (IL-16) was initially described in 1982 as the first T cell chemoattractant. Through interaction with CD4, IL-16 has now been characterized as a chemoattractant for a variety of CD4+ immune cells. Recent in vivo studies have more fully characterized IL-16 as an immunomodulatory cytokine that contributes to the regulatory process of CD4+ cell recruitment and activation at sites of inflammation in association with asthma and several autoimmune diseases. Since its cloning in 1994, IL-16 structure and function have been studied extensively. This review addresses the current data regarding IL-16 protein and gene structure; the expanding list of cells capable of generating IL-16; the direct interaction of IL-16 with its receptor, CD4; and the functional bioactivities of IL-16 as they relate to inflammation and HIV-1 infection. In addition, potential therapeutic modalities for IL-16 relating to inflammation and immune reconstitution in HIV-1 infection are also discussed.     

A new polymorphism in the promoter region of the human interleukin-16 (IL-16) gene

Interleukin 16 (IL-16) is a chemotactic cytokine which binds to CD4 and affects T cell activation. Here we report a novel single nucleotide polymorphism, T to C, in the promoter region of the IL-16 gene in two distinct Asian populations, Japanese and Thai. This mutation occurs at an allele frequency of approximately 22% and 18%, respectively. Although IL-16 potently suppresses replication of human immunodeficiency virus type 1 (HIV-1), we observed no significant difference in the allele frequency of this polymorphism between HIV-1-infected and non-HIV-1-infected individuals in both Asian populations. Since differential IL-16 levels have been reported to be associated with inflammatory diseases such as systemic lupus erythematosus, atopic dermatitis and allergic asthma, it would be of interest to analyze the allele frequency of this mutation in patients with these autoimmune and allergic diseases.     

De novo 16p deletion: ATR-16 syndrome

We describe a child with α-thalassemia ascertained by newborn screening. Evaluation at 9 months of age showed minor anomalies and developmental delay. Chromosomal analysis demonstrated a de novo deletion of the most distal portion of the short arm of chromosome 16, which contains the α-globin genes. Analysis of the α-globin locus by Southern blot analysis did not demonstrate altered band sizes at this locus; however, analysis of the films using densitometry confirmed hemizygosity. This is the fifth reported case of the ATR-16 syndrome (α-thalassemia retardation-16) not complicated by duplication or deletion of other chromosomes. Am. J. Med. Genet. 72:451–454, 1997. © 1997 Wiley-Liss, Inc.     

Trisomy 16 and trisomy 16 mosaicism: A review

A review of all prenatal and postnatal diagnoses of trisomy 16 and trisomy 16 mosaicism was carried out in the context of the current understanding of confined placental mosaicism and uniparental disomy (UPD). The prenatal detection of trisomy 16 cells is associated with a high probability of fetal death, preterm delivery, intrauterine growth retardation, and fetal anomalies. Birth defects were typical of those seen in nonmosaic partial duplications of chromosome 16. Surprisingly, anomalies were sometimes limited to a single organ and included some relatively common isolated defects such as a ventricular septal defect, hypospadias, imperforate anus, inguinal hernia, and clubfoot. The risk for abnormality appeared to be higher in those pregnancies in which trisomy 16 cells were identified in amniotic fluid compared to the detection in chorionic villi samples. Contrary to nonmosaic trisomy 16 with an excess of males, mosaic trisomy 16 shows an excess of female karyotypes. Following the prenatal detection of trisomy 16 cells, aneuploid cells are almost never found in fetal or neonatal lymphocytes. Studies on fibroblasts also often fail to confirm the presence of the abnormal cell line even in cases in which multiple anomalies are present. It is likely that trisomy 16 cells are sometimes present in the early developing embryo even though subsequent cytogenetic studies on fetal or neonatal tissues may not detect any aneuploid cells. UPD can be excluded as a mechanism for those anomalies that are common to mosaic trisomy 16 and nonmosaic partial duplications. The term “occult mosaicism” is suggested to describe the situation in which the presence of an abnormal cell line is suspected on the basis of clinical data but unproven by laboratory analysis. Am. J. Med. Genet. 79:121–133, 1998. © 1998 Wiley-Liss, Inc.     

Duplication of 16p from insertion of 16p into 16q with subsequent duplication due to crossing over within the inserted segment

Two members of a large family had a similar multiple congenital anomalies mental retardation (MCA/MR) syndrome and an identical aberration of chromosome 16. Their mothers, who are first cousins, had a different abnormality of one chromosome 16, which appeared to be an acrocentric. We interpret these findings as an insertion of a segment of 16p into 16q, following a three-break rearrangement and meiotic crossing over. The two abnormal children have a duplication of 16p11→p13. The clinical manifestations of these patients differ from those of previously reported cases of dup(16p).