56例口腔鳞癌患者HPV感染和p53蛋白表达的临床病理学意义

应用免疫组化LSAB法检测56例口腔鳞癌患p53蛋白的表达及变化,用PCR技术检测HPV感染率,探讨人乳头状瘤病毒（HPV）感染及抑癌基因p53在维吾尔族口腔鳞癌患中的异常表达与肿瘤病理生物学特征间关系及临床病理学意义,为维吾尔族口腔鳞癌有效防治提供实验科学依据,本研究得出：（1）免疫组化法检测抑癌基因p53在细胞内的表达可对良恶性病变从分子水平进行评估,并可作为早期诊断及临床治疗口腔鳞癌的分子生物学指标;（2）HPV16、18型感染麦收口腔鳞癌的发生密切相关,可能是口腔鳞癌发生中的重要环节。     

输卵管恶性肿瘤的特点及p53蛋白表达

分析20例原发性输卵管恶性肿瘤的临床特点及p53蛋白表达，结果显示原发性输卵管恶性肿瘤的恶性程度较高及生存期较短者，p53蛋白表达较高。认为p53基因突变参与了该肿瘤的发生，可作为临床判断其恶性程度及患者预后的指标。     

胰腺癌ras p21蛋白表达与AgNORs计数及组织学分级的关系

目的研究胰腺癌ras p21蛋白表达与AgNORs计数及组织学分级的关系。方法用免疫组化法检测了50例胰腺癌组织及50例正常胰腺组织中ras p21蛋白的表达；AgNORs染色技术检测胰腺癌细胞的AgNORs含量；观察肿瘤的组织学分级。结果ras p21蛋自在胰腺癌组织和正常胰腺组织中的表达有显著差异；ras p21蛋白阳性胰腺癌的AgNORs计数比阴性的AgNORs计数明显增多（P〈0．001）：ras p21蛋白表达与肿瘤组织学分级呈显著负相关（r5==0．99，P〈0．001）。结论胰腺癌的发生发展过程包含了ras p21基因的突变。ras p21蛋白表达可反映胰腺癌的恶性程度，是一个有效的判断胰腺癌预后的指标。     

脂肪肉瘤组织中p16、p53蛋白的表达及意义

目的观察脂肪肉瘤组织中p16、p53蛋白的表达并探讨其意义。方法脂肪肉瘤患者32例,行脂肪肉瘤根治性切除术30例,脂肪肉瘤姑息性减瘤术2例。术中取其脂肪肉瘤组织及正常脂肪组织各32例,采用免疫组化SP法检测其p16、p53蛋白。结果脂肪肉瘤、正常脂肪组织中p16蛋白阳性表达率分别为62.50%和100%,p53阳性率分别为68.75%和0,脂肪肉瘤与正常脂肪组织相比,P均〈0.05。随脂肪肉瘤病理分型升高,p16表达下降而p53表达升高,p16与p53蛋白表达呈负相关（r=-1,P均〈0.05）。结论脂肪肉瘤组织中p16蛋白呈低表达,p53蛋白呈高表达,二者表达呈负相关关系,共同参与了脂肪肉瘤的发生、发展。     

p27蛋白在肺腺癌中的表达及临床意义

目的 探讨p27蛋白在肺腺癌的表达及临床意义.方法 应用免疫组化技术检测44例肺腺癌患者的p27蛋白表达,分析p27蛋白表达与性别、年龄、肿瘤大小、临床分期、分化程度和淋巴结转移以及预后的关系.结果 p27蛋白水平与肺腺癌的分化程度相关,与患者的年龄、性别、肿瘤大小、淋巴结转移、TMN分期无关.p27蛋白低表达者的平均生存期（18.6个月）明显低于p27蛋白高表达者（34.5个月）.结论 p27蛋白表达可以作为评价肺腺癌恶性程度和预后的一个重要指标.     

食管癌组织中CtBP1、p16蛋白的表达变化

目的观察食管癌组织中C端结合蛋白（CtBP）1和p16蛋白的表达变化。方法采用免疫组化法检测57例食管癌组织（观察组）及30例癌旁组织（对照组）中的CtBP1和p16蛋白,并分析其与食管癌临床病理参数的关系。结果观察组51例、对照组29例CtBP1蛋白表达阳性,两组CtBP1蛋白阳性表达率相比P〉0.05。观察组30例、对照组24例p16蛋白表达阳性,两组p16蛋白阳性表达率相比P〈0.05。食管癌组织中p16表达与临床分期、淋巴结转移有关（P均〈0.05）,与病理分型无关（P〉0.05）;CtBP1表达与临床分期、淋巴结转移、病理分型均无关（P均〉0.05）。结论食管癌组织中p16蛋白表达下调,CtBP1蛋白表达无明显变化。     

原发性小肠腺癌p16蛋白及PCNA的表达

目的检测p16蛋白和PCNA在原发性小肠腺癌组织、癌旁组织及正常小肠组织中的表达。方法采用SP免疫组化法对36例小肠腺癌及其相应癌旁组织、6例正常小肠组织进行p16蛋白及PCNA的定位观察。结果①原发性小肠腺癌组织中p16蛋白阳性率为88.89％，相应癌旁组织及正常小肠组织中p16蛋白未见表达；原发性小肠腺癌组织中p16蛋白的表达与其分化程度及有无淋巴结转移相关（P〈0.05）；②原发性小肠腺癌组织中PCNA阳性率为61.11％，相应癌旁组织及正常组织PCNA阳性率为28.57％，二者比较P〈0.05；原发性小肠腺癌组织中PCNA的表达与肿瘤部位、浸润深度、分化程度相关（P〈0.05）；③原发性小肠腺癌组织中p16蛋白的表达优于PCNA的表达（P〈0.05）。结论①小肠腺癌中p16蛋白的高表达可能是其癌变过程中的早期事件，有望作为小肠腺癌的免疫标志物；②PCNA可作为判断预后的有效指标；③原发性小肠腺癌组织中p16蛋白的表达优于PCNA的表达，两者联合检测可早期诊断小肠腺癌，判断预后。     

涎腺肿瘤组织中HSP90α和C—mye表达及意义

目的探讨涎腺肿瘤中热休克蛋白90的α亚基（HSP90α）和癌基因C—myc在涎腺肿瘤发生发展中的作用及机制。方法采用免疫组化SP法检测17份恶性（恶性组）和41例良性涎腺肿瘤组织（良性组）中HSP90α、C-myc的表达。结果恶性组HSP90ct阳性率显著高于良性组（P均〈0．05）,且从腮腺、颌下腺到小涎腺的阳性强度有增加趋势（Fishergexact=0．008）。恶性组C—myc表达均较强,其阳性率显著高于良性组（P=0．028）。C-myc表达与HSP90et呈正相关（r=0．278,P均〈0．05）;恶性组HSP90α阳性者C—myc的阳性率显著高于良性组（P〈0．05）。结论HSP90α和C—myc可促进涎腺恶性肿瘤的发生、发展。HSP90α可能通过C—myc共同促进涎腺肿瘤的发生发展和恶性转化。     

腮腺腺样囊性癌组织p53蛋白的表达及意义

腮腺腺样囊性癌是涎腺肿瘤中最为常见的恶性肿瘤。本研究通过免疫组织化学方法检测92例腮腺良恶性肿瘤标本p53蛋白的表达,探讨其与腮腺肿瘤生物学特性的关系及其临床意义。1材料与方法1.1材料选择我院肿瘤外科手术切除并经病理组织学确诊的腺样囊性癌标本72例,术前均未经放疗或化疗,并按病理分级,其中腺样囊性癌Ⅰ级16例,Ⅱ级22例,Ⅲ级20例,Ⅳ级14     

p15蛋白在子宫内膜组织中的表达及意义

目的 观察p15蛋白在不同子宫内膜组织中的表达及意义。方法应用免疫荧光技术检测p15蛋白在不同子宫内膜组织中的表达,并分析其与病变类型的相关性。结果p15在15例单纯性子宫内膜增生组织均表达阴性,在16例非典型子宫内膜增生组织中9例阳性、其中1例（6．25％）过度表达,在29例子宫内膜样腺癌组织均阳性、其中16例过度表达（58．17％）,在15例非子宫内膜样腺癌组织均阳性、其中12例过度表达（80％）,表达阳性率单纯性子宫内膜增生组织〈非典型子宫内膜增生组织〈子宫内膜样腺癌组织〈非子宫内膜样腺癌组织（P〈0．05）。结论p15蛋白在子宫内膜组织中的表达与病变组织类型有关,对其进行监测有利于对子宫内膜恶性疾病进行早期诊治。     

p16基因启动子区甲基化在人嗜铬细胞瘤和副神经节瘤中的变化

目的 检测嗜铬细胞瘤(PHEO)和副神经节瘤(PGL)中p16基因突变和启动子区DNA甲基化改变,分析其与患者临床特征之间的关系.方法收集34例(PHEO 20例、PGL14例)组织标本及患者临床资料,通过甲基化特异性PCR(MSP)测定p16基因启动子区甲基化状态,DNA测序检测基因序列以及RT-PCR方法测定其mRNA表达.结果 (1)34例肿瘤组织中未发现p16基因纯合缺失及点突变;(2)35.3%(12/34)的患者存在p16基因高甲基化,p16基因甲基化阳性标本中,PHEO和PGL分别占25%和75%,两者差异有统计学意义(P=0.005);p16基因甲基化在恶性、单发肿瘤、发病年龄早的亚组中有增高趋势(P＞0.05);(3)甲基化与非甲基化肿瘤组织之间p16 mRNA表达无统计学差异;不同特点的肿瘤中其mRNA表达亦无统计学差异,但恶性肿瘤p16 mRNA表达与良性肿瘤相比有下降的趋势(0.83±0.65对1.12±0.81,P=0.278).结论人PHEO和PGL中,p16基因纯合缺失和突变并不常见,但p16基因启动子区甲基化是其失活的主要形式.     

人类端粒酶逆转录酶hTERT Ki-67及p27kip1在嗜铬细胞瘤组织的表达及意义研究

目的研究人端粒酶逆转录酶(hTERT)、Ki-67及p27kip1的表达在嗜铬细胞瘤发生与发展中的作用和作为预测生物学行为标志物的价值。方法采用免疫组织化学方法检测hTERT、Ki-67及p27kip1在2000—2004年广西医科大学第一附属医院病理科的45例嗜铬细胞瘤和神经节细胞瘤及9例正常肾上腺组织中的表达。结果hTERT蛋白的表达在良性(3/31例)和可疑恶性(6/7例)以及良性与恶性肿瘤(5/7例)间的差异均有统计学意义(P<0.01)。31例良性肿瘤中26例未检测到Ki-67,而恶性肿瘤和可疑恶性肿瘤均为阳性;Ki-67与hTERT的表达呈正相关性(r=0.544,P<0.01)。恶性和可疑恶性肿瘤中未检测到p27kip1,5例良性肿瘤为阳性,所有正常肾上腺髓质标本均可检测到p27kip1的表达。p27kip1与hTERT的表达无相关性。结论端粒酶的激活在恶性嗜铬细胞瘤和神经节细胞瘤的发生发展中起着重要作用,在细胞周期调控中端粒酶可能存在不同的激活途径。hTERT和Ki-67的检测可作为鉴别良恶性嗜铬细胞瘤的手段。     

P53 mutation but not p16/MTS1 mutation occurs in intraductal papillary mucinous tumors of the pancreas

BACKGROUND/AIMS: Intraductal papillary mucinous tumors of the pancreas are rare lesions, which typically show a benign clinical course. However, some of these tumors have a malignant nature and grow in an invasive manner. The purpose of the study was to determine the prevalence of p53-, p16/MTS1- and K-ras mutations in benign and malignant intraductal papillary mucinous tumors with intent to value their importance for tumor progression. METHODOLOGY: Thirteen different archival tumor specimens were obtained at the Department of Pathology, University of Ulm. Three cases showed an invasive component of the tumor. Genomic DNA was extracted after laser capture microdissection of tumor cells from paraffin-embedded tissue sections. The corresponding sequences of p53 (exon 5, 6, 7, 8) and p16/MTS1 (exon 2) were amplified by polymerase chain reaction and subjected to single strand conformation polymorphism analysis. Codon 12 of K-ras was analyzed by the enrichment polymerase chain reaction-restriction fragment length polymorphism method. Positive samples were further investigated by sequencing. RESULTS: K-ras mutations occurred in benign and malignant intraductal papillary mucinous tumors (4/13), whereas an alteration of the coding p53 gene sequence could only be detected in the intraductal and invasive component of one malignant tumor. None of the tissue specimens revealed mutations in exon 2 of p16/MTS1. CONCLUSIONS: In contrast to K-ras mutations, alterations in the p53 gene may characterize ductal papillary mucinous carcinomas, which could be of major interest for their early diagnosis. The lack of mutations in the p16/MTS1 gene suggests that other genes may be involved in the formation of intraductal papillary mucinous neoplasias.     

流式细胞学DNA分析在良、恶性涎腺多形性腺瘤中的应用价值

目的　探讨流式细胞学 DNA分析 (FCM)对良、恶性涎腺多形性腺瘤的临床价值。方法　采用流式细胞仪测定 5 0例良性涎腺多形性腺瘤、18例恶性涎腺多形性腺瘤和 10例正常涎腺石蜡包埋组织的 DNA倍体及细胞增殖活性 ,分析其变化与预后的关系。结果　正常涎腺组织 DNA皆为二倍体 ;良性涎腺多形性腺瘤 DNA二倍体率为 84 % (42例 ) ,异倍体率 16 % (8例 ) ;恶性涎腺多形性腺瘤分别为 6 1% (11例 )、39% (7例 ) ,与良性者比较有显著性差异 (P<0 .0 5 )。结论　 FCM诊断良、恶性涎腺多形性腺瘤具有一定价值 ,其应用应与形态学检查相结合。     

A joint detection of CEA and CA-50 levels in saliva and serum of patients with tumors in oral region and salivary gland

Objective  To detect the levels of carcinoembryonic antigen (CEA) and carcinoma associated antigen CA-50 in the patients with oral or salivary malignant tumors. Methods  The concentrations of salivary CEA and CA-50 were assayed in 80 patients of oral and salivary malignant tumors, 40 patients of benign tumors and 80 health controls. In 80 patients with malignant tumors, serum CEA and CA-50 were also assayed by enzyme-linked immunoabsorbent assay and immunoradiometric analysis, respectively. Results  Salivary CEA and CA-50 levels were significantly higher in malignant tumors than in benign tumors and in health controls, respectively (P < 0.001). Only 7 cases and 3 cases of 80 patients with malignant tumors were found having increased serum CEA and CA-50 levels, respectively. Conclusions  The measurement of CEA and CA-50 levels in saliva were more sensitive than in serum. This may be more useful as prognostic indicators in early diagnosis of oral and salivary malignant tumors.     

T-helper Type 1 and 2 Cytokine Levels in Patients with Benign and Malignant Salivary Gland Tumors

Background: Salivary gland tumors are among malignancies that have high recurrence rate. Immune responses in salivary gland tumors have not been well elucidated. T helper type 1 (Th1) and Th2 cytokines have been reported to play a role in the outcome of head and neck cancers. Objective: To evaluate the serum levels of interferon gamma (IFN- γ), as the hallmark of Th1 cytokines, and interleukin-4 (IL-4), as the hallmark of Th2 cytokines, in patients with benign and malignant salivary gland tumors in comparison with healthy controls. Methods: Fifty patients with benign and 14 patients with malignant salivary gland tumors, as well as 23 healthy individuals were recruited. Serum levels of IFN-γ and IL-4 were measured using ELISA method. Nonparametric tests were used for data analysis. Results: Serum levels of IFN-γ and IL-4 were found not to be significantly different in patients compared to the control group (0.68 ± 0.29 vs. 1.03 ± 0.57 pg/ml, p=0.58 for IFN-γ, 4.57 ± 1.57 vs. 4.41 ± 1.31 pg/ml, p=0.28 for IL-4). IFN-γ and IL-4 serum levels were also not significantly different between patients with benign and malignant salivary gland tumors (p=0.54 and p=0.86, respectively). Conclusion: The systemic levels of IL-4 and IFN-γ seem not to be associated with salivary gland tumor in our study. Investigation of other cytokines produced by Th1 and Th2 cells are warranted.     

p21 and p27 immunoexpression in gastric well differentiated endocrine tumors （ECL-cell carcinoids）

INTRODUCTION Carcinoid tumors arise from proliferating enter- ochromaffin-like cells (ECL) of fundus. Elevated plasma gastrin levels are responsible of the neoplastic changes in these cells, but neoplastic transformation can also be observed in absence of…     

Low frequency of p16(INK4a) alterations in insulinomas

BACKGROUND/AIMS: The molecular mechanisms contributing to the tumorigenesis of insulinomas are poorly understood. Disruption of the cell cycle due to inactivation of the p16(INK4a) tumor-suppressor gene was identified in a variety of human tumors, including gastrinomas and nonfunctioning endocrine pancreatic carcinomas. In this study the role of p16(INK4a) in the tumorigenesis of insulinomas was evaluated. METHODS: Seventeen insulinomas (14 benign, 3 malignant) were analyzed for genetic alterations in the p16(INK4a) tumor-suppressor gene by SSCP, PCR-based deletion and methylation-specific assays. p16 expression was determined by immunohistochemistry. RESULTS: One malignant insulinoma showed a homozygous deletion of p16(INK4a) and another two benign insulinomas revealed aberrant methylation of the p16(INK4a) promoter region. All three tumors lacked p16 expression according to immunohistochemistry. None of the insulinomas carried intragenic p16(INK4a) mutations. In total, 17% of insulinomas had p16(INK4a) alterations. CONCLUSIONS: The p16(INK4a) tumor-suppressor gene contributes to tumorigenesis in only a small subset of insulinomas.     

Expression of Jun activation domain-binding protein 1 and Ser10 phosphorylated p27 protein in human epithelial ovarian carcinoma

Purpose  The aim of the present study was to examine whether Jab1 expression is correlated with p27 protein and its phosphorylation status as well as how it might be clinically relevant in epithelial ovarian carcinoma. Using ovarian carcinoma cell line HO-8910 to confirm and extend the findings. Methods  Immunohistochemical and Western blot analysis were done in 70 cases of epithelial ovarian cacinoma and HO-8910 cells. Results  Jab1 overexpression was detected in 84.3% (59 of 70) of malignant tumors and 31.6% (6 of 19) of benign tumors. A positive correlation between Jab1 and cytoplasmic p27 as well as Ser10 phosphorylated p27 was found in malignant ovarian tumors. In addition, patients displaying overexpression of Jab1, cytoplasmic p27 and Ser10 phosphorylated p27 were significantly associated with unfavorable clinicopathologic variables. Transfection with Jab1 in HO-8910 cells resulted in decreased p27 expression and this reduction was sensitive to 26S proteasome inhibitors. Overexpression of Jab1 caused p27 nuclear export and dissociate from Cdk2/Cyclin complex. What is more, increased expression of a phosphorylated histone H1 in the immune-complex obtained from Jab1 transfected HO-8910 cells was also observed. Conclusions  Jab1, as a negative regulator of p27, may be associated with the progression and prognosis of epithelial ovarian tumors. You Wang and Yuchan Wang both contributed equally to this work.