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。     

p53蛋白在大肠肿瘤组织中表达的意义

ｐ５３蛋白在大肠肿瘤组织中表达的意义陈大伟，高瀚，王元和，陈泳莲，叶挺军笔者用免疫组织化学方法，检测ｐ５３蛋白在正常大肠粘膜、大肠腺瘤和大肠腺癌组织中表达，研究ｐ５３蛋白表达在大肠癌演变中的作用以及与临床病理关系。材料与方法一、临床资料本研究共收集２...     

p53在人和小鼠口腔鳞状细胞癌组织中表达的比较

目的比较p53在人和小鼠正常口腔黏膜、口腔异常增生组织、口腔鳞状细胞癌(简称鳞癌)组织中的表达及意义。方法采用免疫组织化学方法分别检测人和小鼠各8例口腔正常黏膜,各8例口腔异常增生组织,各8例口腔鳞癌组织中p53的表达情况。结果人口腔正常黏膜p53表达率为0.0%(0/8),口腔异常增生组织p53表达率37.5%(3/8)、口腔鳞癌p53表达率62.5%(5/8);小鼠正常口腔黏膜p53表达率为0(0/6),口腔异常增生组织p53表达率为50.0%(4/8),口腔鳞癌p53表达率为75.0%(6/8)。结论 p53蛋白阳性表达在人和小鼠保持一致性,均随病理恶性程度升高而增加。小鼠口腔鳞癌模型与人类口腔鳞癌的发生发展具有相似性。     

PCNA及P53蛋白在口腔鳞癌组织中的表达及意义

增殖细胞核抗原(PCNA)也称周期蛋白。是反映细胞增殖分数和所处周期的客观指标，可用于判断肿瘤的恶性程度及预后，亦能较好地反映肿瘤细胞的增殖状态。P^53基因是一种重要的肿瘤抑制基因，其突变与肿瘤的发生发展密切相关。2002年1月至2003年12月，我们用免疫组织化学染色技术对49例口腔鳞癌组织的PCNA和P^53基因蛋白进行检测和分析，旨在探讨两项指标与此类肿瘤的诊断、鉴别诊断及病理分级的关系。     

口腔鳞癌组织中 p73、p15蛋白的表达变化及意义

目的：观察口腔鳞癌组织中p73、p15蛋白的表达变化,并探讨其意义。方法采用免疫组化SP法检测20例份口腔正常黏膜组织（对照组）、35例份扁平苔藓组织（扁平苔藓组）、50例份鳞癌组织（鳞癌组）中p73、p15蛋白,并分析鳞癌组中两指标的相关性。结果鳞癌组、扁平苔藓组、对照组p73阳性率分别为82．00％、54．29％、15．00％,p15阳性率分别为42．00％、100．00％、100．00％,两两比较,P均＜0．05;鳞癌组Ⅰ、Ⅱ、Ⅲ级p73阳性率分别为70．83％、90．00％、100．00％,p15阳性率分别为54．17％、35．00％、16．67％,两两比较,P均＜0．05。鳞癌组p73、p15蛋白表达呈负相关（r＝－0．932,P＜0．05）。结论口腔鳞癌组织中p73蛋白表达升高,p15蛋白表达降低,两者在口腔鳞癌发生、发展过程当中起到相互拮抗的作用。     

p53和Bcl-2蛋白在舌鳞癌组织中的表达及意义

目的 研究p53和Bcl-2蛋白在舌鳞癌和癌前病变中的表达及意义。方法 采用免疫组化SP法检测38例舌鳞癌（A组）、20例13腔癌前病变（B组）及10例正常口腔舌上皮组织（C组）中p53和Bcl-2蛋白的表达情况。结果比较A、B、C三组,p53和Bcl-2蛋白的表达在A组与C组、B组与C组之间,P均〈0．05,在A组与B组之间,P〉0．05;ps3蛋白异常表达在淋巴结转移组显著高于无转移组,P〈0．05;Bcl-2蛋白高表达与p53蛋白高表达之间无相关性,P〉0．05。结论p53和Bcl-2蛋白高表达与舌鳞癌的发生、发展密切相关。     

抑癌基因p53与p16在胆囊癌的表达及意义

本研究,采用免疫组化法测定胆囊癌和胆囊良性病变标本的抑癌基因ｐ53与ｐ16蛋白表达,分析其在胆囊癌发生和发展中的作用以及和预后的关系。材料与方法一、标本来源收集本院近来手术的24例胆囊癌、20例胆囊腺瘤和18例慢性胆囊炎。胆囊癌根据Ｎｅｖｉｎ分期,Ｓ1、Ｓ2、Ｓ3共11例,Ｓ4、Ｓ5共13例。病理分级:Ⅰ级7例,Ⅱ级9例,Ⅲ级8例。所有标本均为石蜡包埋,作4μｍ连续切片。二、免疫组化法ｐ16抗体Ｃ20为ＳａｎｔａＣｒｕ2Ｂｉｏｔｅｃｈ产品,ｐ53抗体Ｄｏ7为Ｄａｋｏ产品。免疫组化采用Ｅｎｖｉｓｉｏｎ法,微波加热后进行抗原修复和暴露。以…     

Pgp、MRP和p53蛋白在肺癌组织中的表达及其意义

Ｐｇｐ、ＭＲＰ均属于ＡＴＰ结合盒式超家族 ,有药物外排泵的作用 ,它们的过表达与多种肿瘤的多药耐药密切相关 ,但在肺癌耐药过程中所起的作用 ,研究结果并不一致 ;有文献报道 ,ｐ5 3异常与Ｐｇｐ过表达亦有一定相关性。本研究通过检测肺癌组织中Ｐｇｐ、ＭＲＰ、ｐ5 3的表达 ,探讨三者在肺癌中可能的作用及相互间的关系。一、对象与方法1 .对象 :选择经病理证实的 31例原发性肺癌和相应的远癌肺组织新鲜手术标本 ,31例石蜡包埋 ,2 9例 (缺 2例腺癌 ) - 70℃保存。所有患者在术前均未接受过化疗或放疗。31例肺癌中小细胞肺癌 (ＳＣＬＣ) 6…     

Association of p53/p21 expression with cigarette smoking and prognosis in esophageal squamous cell carcinoma patients

factors,such as cigarette smoking,in esophageal squamous cell carcinoma(ESCC)in northeastern Iran,a region with a high incidence of ESCC.METHODS:The expression of p53 and p21 proteins was investigated immunohistochemically in tumor tissue from 80 ESCC patients and in 60 available paraffinembedded blocks of adjacent normal specimens from the cases,along with normal esophageal tissue from 80 healthy subjects.RESULTS:Positive expression of p53 protein was detected in 56.2%(45/80)of ESCC cases,and in none of the normal esophageal tissue of the control group(P<0.001).Furthermore,73.8%(59/80)of ESCC cases and 43.8%(35/80)of controls had positive expression of p21 protein(P<0.001).Cigarette smoking was significantly associated with p53 over-expression in ESCC cases(P=0.010,OR=3.64;95%CI:1.32-10.02).p21 over-expression was associated with poorer clinical outcome among the ESCC patients(P=0.009).CONCLUSION:Over-expression of p53 in association with cigarette smoking may play a critical role in ESCC carcinogenesis among this high-risk population of northeastern Iran.Furthermore,p21 over-expression was found to be associated with poor prognosis,specifically in the operable ESCC patients.     

COX-2, MMP-7 expression in oral lichen planus and oral squamous cell carcinoma

ObjectiveTo observe cyclooxygenase (COX)-2 expression in normal oral mucosa (NOM), oral lichen planus (OLP) and oral squamous cell carcinoma (OSCC) and explore its significance in the incidence of oral cancer.MethodsThe immunohistochemical method and RT-PCR method were applied to detect the expression of COX-2 and MMP-7 in 10 cases with NOM, 33 cases of with OLP and 38 cases with OSCC.ResultsThe expression of COX-2 mRNA in OSCC tissues (68.4%, 26/38) was significantly higher than in the OLP (24.2%, 8/33) and NOM (0.0%, 0/10) (P<0.01). The expression of MMP-7 mRNA in OSCC tissues (65.8%, 25/38) was significantly higher than in the OLP (30.3%, 10/33) and NOM (0.0%, 0/10) (P<0.01). The expression of MMP-7 in OLP was significantly higher than in the NOM (P<0.05). There was no significant expression of COX-2 protein in NOM, and the positive rate was 42.4% (14/33) and 89.5% (34/38) in OLP and OSCC group, respectively. The COX-2 expression in cancer tissues was significantly higher than in NOM and OLP (P<0.05). The MMP-7 protein expression in cancer tissues (84.2%, 32/38) was significantly higher than in NOM (10.0%, 1/10) and in OLP (42.4%, 14/33), and the positive rate in OLP was significantly higher than in NOM (P< 0.01). The COX-2 expression was associated with clinical stage (P<0.05), the MMP-7 expression was associated with clinical stage and lymph node metastasis (P<0.05). The expressions of COX-2 and MMP-7 mRNA were positively correlated with OSCC.ConclusionsThe abnormal expressions of COX-2 and MMP-7 are closely related to the biological behavior of OSCC, the MMP-7 may be induced by COX-2, and further lead to the invasion and metastasis of OSCC.     

A study on p53 gene alterations in esophageal squamous cell carcinoma and their correlation to common dietary risk factors among population of the Kashmir valley

AIM: To systematically examine the extent of correlation of risk factors, such as age, consumed dietary habit and familial predisposition with somatic Tp53 molecular lesion causal to elevate carcinogenesis severity of esophageal squamous cell carcinoma (ESCC) among the Kashmiri population of Northern India. METHODS: All cases (n=51) and controls (n = 150) were permanent residents of the Kashmir valley. Genetic alterations were determined in exons 5-8 of Tp53 tumor suppressor gene among 45 ESCC cases histologically confirmed by PCR-SSCP analysis. Data for individual cancer cases (n = 45) and inpatient controls (n = 150) with non-cancer disease included information on family history of cancer, thirty prevailing common dietary risk factors along with patient's age group. Correlation of genetic lesion in p53 exons to animistic data from these parameters was generated by Chi-square test to all 45 histologically confirmed ESCC cases along with healthy controls. RESULTS: Thirty-five of 45 (77.8%) histologically characterized tumor samples had analogous somatic mutation as opposed to 1 of 45 normal sample obtained from adjacent region from the same patient showed germline mutation. The SSCP analysis demonstrated that most common p53 gene alterations were found in exon 6 (77.7%), that did not correlate with the age of the individual and clinicopathological parameters but showed significant concordance (P<0.05) with familial history of cancer (CD=58), suggesting germline predisposition at an unknown locus, and dietary habit of consuming locally grown Brassica vegetable "Hakh" (CD=19.5), red chillies (CD=20.2), hot salty soda tea (CD = 2.37) and local baked bread (CD=1.1). CONCLUSION: Our study suggests that somatic chromosomal mutations, especially in exon 6 of Tp53 gene, among esophageal cancer patients of an ethnically homogenous population of Kashmir valley are closely related to continued exposure to various common dietary risk factors, especially hot salty tea, meat, baked bread and "Hakh", that are rich in nitrosoamines and familial cancer history.     

食管鳞癌组织p16基因调控区甲基化及其蛋白表达研究

目的探讨p16基因在食管癌变过程中表达缺失与其启动子区甲基化的关系。方法采用MSP免疫组化方法,检测环太行山地区45例食管鳞癌患者癌组织p16基因启动子区甲基化状态及蛋白表达情况。结果p16基因在癌组织中表达异常41例（91．1％）,间变组织中表达异常38例（84．4％）,发生纯合型甲基化的组织分别为33例（73．3％）（癌组织）和32例（71．1％）（间变组织）,而其周围正常组织26例（57．8％）均发生了p16启动子区的杂合型甲基化。p16基因纯合型甲基化与癌组织、间变组织、p16蛋白表达缺失相关（P〈0．05）。结论该地区食管癌组织p16基因在癌前病变中p16启动子区即发生了纯合型甲基化、食管癌变的早期事件。p16基因启动子区甲基化可单独影响p16蛋白的正常表达。     

肺鳞癌组织Mdm2蛋白表达p53基因突变相关性研究

目的探讨原发性肺鳞癌与Ｍｄｍ２蛋白表达、ｐ５３基因突变之间的相关性。方法采用ＳＰ免疫组织化学方法和银染聚合酶链式反应单链构象多态性（银染ＰＣＲＳＳＣＰ）方法检测手术切除、经病理证实的４５例原发性肺鳞癌组织及癌旁肺组织中Ｍｄｍ２蛋白表达和ｐ５３基因突变情况。结果免疫组织化学检测的４５例肺鳞癌组织Ｍｄｍ２蛋白阳性率为６２％（２８／４５）,２例癌旁肺组织中Ｍｄｍ２蛋白呈弱阳性表达,免疫组织化学方法结合银染ＰＣＲＳＳＣＰ检测４５例肺癌组织ｐ５３基因突变,阳性率为５１％（２３／４５）,４５例癌旁肺组织未检测到ｐ５３基因突变。（１）肺鳞癌与ｐ５３基因突变有明显相关性（Ｐ＜０．０５）。（２）肺鳞癌与Ｍｄｍ２基因产物过度表达有明显相关性（Ｐ＜０．０５）。（３）Ｍｄｍ２蛋白过度表达与ｐ５３基因突变复合存在和肺鳞癌淋巴转移（６６％,１０／１５）有明显相关性（Ｐ＜０．０５）。结论Ｍｄｍ２蛋白过度表达与ｐ５３基因突变是临床估计患者预后重要的分子生物学指标     

Expressions of p53, VEGF C,p21: could they be used in preoperative evaluation of lymph node metastasis of esophageal squamous cell carcinoma?

The prognosis of esophageal squamous cell carcinoma is primarily determined by staging. Although radiological methods have revealed lymph node metastasis preoperatively, these radiological findings cannot be correlated with pathological staging. The aim of this study was to compare the expressions of p53, vascular endothelial growth factor C (VEGF C) and p21 with lymph node metastasis in preoperative endoscopic biopsy and postoperative resection material. Tissue samples were taken from 40 patients who had undergone endoscopic biopsies and radical esophagectomies. The expressions of p53, VEGF C and p21 proteins in these sections were immunohistochemically examined. The expression of each antibody was characterized as a negative or positive reaction according to the pattern and intensity of semiquantitative immunostaining. The staining pattern of antibodies was divided into three groups: < 10% cancer cells were accepted to be (-), 10-50% were (+), heterogenous and > 50% were (+ +), homogenous. For each antibody, statistical correlation with conventional prognostic parameters such as localization, microscopic grade, stage, pathological lymph node metastasis and survival, were investigated. p53 expression was observed in 65.5% (19/29) of lymph node positive cases, whereas p53 was in 50% (20/40) of cases. VEGF C was in 65% (26/40) and p21 was in 15% (6/40) of cases. p53 has the specificity of 90.9% and sensitivity rate of 65.5% in detecting lymph node metastasis and positive predictive value was 95%. Expression of p53 was significantly correlated with stage and lymph node metastasis (P = 0.02 and P = 0.03, respectively). Prediction of lymph node metastasis by p53 was correlated independently and in coexpression with VEGF C (P < 0.01). There was no relation detected between p21 and other parameters. In esophageal squamous cell carcinoma (SCC), p53 and VEGF C expressions were correlated with pathologically positive lymph nodes. When preoperative staging has been insufficient in esophageal carcinoma cases, immunohistochemical analysis of p53 and VEGF C staining in tissues could be an aid to clinicians regarding lymph node metastasis.     

P53 gene codon 72 polymorphism and risk of esophageal squamous cell carcinoma: a case/control study in a Chinese population

SUMMARY.  The aims of this study were to investigate whether p53 gene codon 72 polymorphism was a biomarker associated with esophageal squamous cell carcinoma (ESCC) and its relationship with smoking status in China. The p53 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism among 673 patients with ESCC and 694 healthy controls. The association between p53 genotypes and risk of developing ESCC was estimated by odds ratios (OR) and their 95% confidence intervals (CIs) computed by logistic regression. Compared with Arg/Arg homozygotes, Pro/Pro homozygotes had a nearly twofold increased risk (adjusted OR, 1.83; 95% CI, 1.35–2.48). For the Pro/Arg heterozygotes, there was no evident increased risk (adjusted OR, 1.01, 95% CI, 0.78–1.30). Furthermore, the risk associated with the Pro/Pro variant genotype was more pronounced in younger patients at diagnosis (= 45 years) (OR, 7.4; 95% CI, 1.44–37.89, P  = 0.02), in women (OR, 3.15; 95% CI, 1.52–4.53, P  = 0.02) and in non-smokers (OR, 2.49; 95% CI, 1.58–3.94) and light smokers (OR, 2.13; 95% CI, 1.15–3.93). But tests for homogeneity between smoking-related OR showed no significant differences ( P  = 0.4). The p53 gene codon 72 Pro/Pro genotype was significantly associated with the increased risk of ESCC in a Chinese mainland population and may be an independent factor in susceptibility to ESCC. The association was especially noteworthy in women and in younger patients.