膀胱癌中PGP、MDM2、p53基因表达的意义

目的探讨膀胱癌组织中Pgp、MDM2、p53基因表达的意义。方法采用免疫组织学方法检测83例膀胱移行细胞癌中Pgp、MDM2、p53基因表达的情况。结果Pgp阳性表达率为71.08%,p53阳性表达率为50.6%,MDM2阳性表达率59.03%,MDM2阳性表达与膀胱癌病理分级及临床分期呈负相关(γ=-0.263,P=0.016及γ=-0.388,P=0.001);p53阳性表达与膀胱癌病理分级呈正相关(γ=0.492,P=0.001);Pgp阳性表达与其病理分级及临床分期无相关性;Pgp、MDM2、p533种蛋白表达间无相关性。AI、p53、MDM2表达与患者5年生存率有关。结论检测Pgp可指导膀胱癌化疗药物的选择;运用膀胱癌临床分期及病理分级并检测其p53、MDM2表达,可判断膀胱移行细胞癌的预后。     

HPV16/18DNA和p53、RB、MCM7蛋白在乳腺癌中的表达及意义

目的:探讨HPV16/18DNA和p53、RB、MCM7蛋白在乳腺癌中的表达及意义.方法:用原位杂交和免疫组织化学EnVision法检测30例正常乳腺组织、30例乳腺腺病、30例乳腺不典型导管上皮增生、20例乳腺导管原位癌和68例乳腺癌组织标本中HPV16/18DNA和p53、RB、MCM7蛋白的表达.结果:乳腺癌组织中HPV16/18DNA的阳性率为58.8％,明显高于正常乳腺、乳腺腺病和乳腺不典型导管上皮增生组,差异有统计学意义(P＜0.05).在不典型导管上皮增生、导管原位癌和乳腺癌组织中HPV16/18DNA与p53和RB蛋白的表达均呈负相关(P＜0.05),而癌组中HPV 16/18DNA与MCM7蛋白表达呈正相关(r=0.750,P＜0.05).癌组中组织学G2、G3级,pTNM Ⅱ、Ⅲ期以及有淋巴结转移组中HPV16/18DNA和MCM7蛋白的阳性表达率均显著高于组织学G1级和pTNM Ⅰ期以及无淋巴结转移组(P＜0.05);与之相反,p53和RB蛋白的阳性表达率则显著降低(P＜0.05).结论:HPV16/18感染通过对p53、RB和MCM7蛋白表达调控的影响可能在高危型HPV感染后乳腺癌的发生、发展及转移进程中起到重要的作用.通过联合检测它们在乳腺癌及癌前病变中的表达以评价临床疾病进展和肿瘤生物学行为.     

HPV16/18在膀胱癌中表达及其与bFGF、cyclinD1和cyclinE的相关关系

目的探讨人乳头瘤病毒(HPV)16/18与膀胱癌发病之间关系及其作用机制.方法应用免疫组化方法检测78例膀胱癌标本和11例正常膀胱组织中HPV16/18、碱性成纤维细胞生长因子(bFGF)、细胞周期蛋白(cyclin)D1和cyclinE的表达及相关关系.结果膀胱癌中HPV16/18阳性率为65.4%,显著高于正常的27.3%;而且与肿瘤病理分级、分期相关,但与肿瘤复发无相关.膀胱癌中HPV16/18与bFGF及cyclinD1表达之间有显著相关性,但与cyclinE表达之间无显著相关性.结论HPV16/18感染参与膀胱癌发病过程,而且通过多途径发挥作用.     

宫颈腺癌p53、HPV16/18-E6蛋白和ER的表达及其临床意义

目的　探讨宫颈腺癌组织中 p5 3蛋白、HPV16 / 18 E6蛋白及ER的表达及其临床意义。 方法　采用免疫组织化学S P法对 6 3例宫颈腺癌组织进行p5 3蛋白、HPV16 / 18 E6蛋白及ER检测。结果　 6 3例宫颈腺癌中p5 3、HPV16 / 18 E6蛋白和ER阳性表达率分别为为 5 2 .3%、31.7%和 4 9.2 %。p5 3表达与肿瘤病理分级、临床分期 (Ⅰ、Ⅱ、Ⅲ期 )有关。HPV16 / 18 E6、ER的表达与宫颈腺癌的病理学分级、临床分期无关 ,但与 p5 3表达呈负相关 (P <0 .0 1) ,HPV16 / 18 E6、ER在宫颈腺癌中的表达呈正相关 (P <0 .0 1)。结论　随宫颈腺癌组织病理分级和临床分期增高p5 3阳性表达率逐渐增高 ,可能与 p5 3突变有关 ,部分宫颈腺癌的发病可能与HPV16 / 18 E6蛋白过度表达有关。部分宫颈腺癌可能属于激素依赖性 ,雌激素可能有协同HPV致癌的作用。     

人乳头瘤状病毒感染与抑癌基因p16突变在食管鳞癌中的研究

目的本研究旨在应用聚合酶链反应技术(PCR)联合DNA探针技术对河北省中南部地区食管鳞癌患者人乳头瘤病毒(HPV)感染情况进行研究,以明确二者之间的关系;同时应用单链构象多态性(SSCP)技术对标本p16基因第二外显子突变进行初筛,以明确其在食管癌发病过程中的变化以及HPV感染与p16基因突变的关系。方法对47名河北省中南部地区食管鳞癌切除术患者的癌组织(实验组)以及37名相同地域健康志愿者食管黏膜组织(对照组)进行取材,提取DNA进行HPV分型检测,同时以HPV E6基因引物对标本DNA HPV感染情况进行复检;除试剂盒阳性、阴性对照外,同时采用HPV阳性宫颈癌组织做阳性对照,DEPC水做阴性对照。HPV感染检测完成之后,以p16基因第二外显子引物对组织DNA进行SSCP分析,判断HPV感染时是否伴有p16基因突变。统计学分析采用SPSS13.0软件完成,其中以病理分期为标记分组,采用K个独立样本的非参数检验方法检验不同病理分期的p16基因是否呈现差异;采用pearson相关分析检验p16基因第二外显子在食管鳞癌中与性别、年龄、吸烟史、饮酒史、家族史及淋巴结转移的关系。结果食管鳞癌患者中HPV感染率0%,正常对照组HPV感染率为0%,试剂盒阳性对照呈现阳性,宫颈癌标本HPV感染呈现阳性;复检食管癌患者中HPV E6基因为0%,正常对照组HPV E6基因为0%,宫颈癌标本HPV E6基因为阳性,此结果和试剂盒检测结果一致。食管鳞癌患者中p16第二外显子基因缺失率为0%,基因突变率为44.7%;正常对照组p16第二外显子基因缺失率为0%,基因突变率为0%。p16基因突变与不同病理分期的食管鳞癌的关系中,渐近显著性P值为0.035,卡方值为6.691,认为病理分期越晚,p16第二外显子基因突变率越高;Pearson相关分析中,p16基因第二外显子在食管鳞癌中与性别、年龄、吸烟史、饮酒史、家族史及淋巴结转移的渐进显著性P值分别为0.496、0.143、0.000、0.547、0.113、0.005;以HPV感染为标记分组,检验HPV感染与p16基因变异(Fisher确切概率法)P0.05,无统计学意义。结论 (1)河北省中南部地区HPV感染与食管鳞癌无关,HPV感染可能不是食管鳞癌的病因。(2)p16基因第二外显子基因变异与食管鳞癌有关。食管鳞癌病理分期越晚,p16基因第二外显子突变越明显。(3)p16基因第二外显子突变与患者吸烟史及淋巴结转移情况有关。(4)HPV感染可能并非食管鳞癌中p16基因第二外显子突变的原因。     

p53、人半翼基因在宫颈癌前病变及宫颈癌中的表达及相关性分析

目的 探讨p53、人半翼基因(hWAPL)在宫颈癌前病变及宫颈癌中的表达及相关性.方法 选取67例低级别宫颈上皮内瘤变(CIN)患者(CINⅠ)、58例高级别CIN患者(CINⅡ～Ⅲ)、42例宫颈癌患者和39例宫颈炎患者,取相应的CIN组织、宫颈癌组织和正常宫颈组织,免疫组化法检测HPV16/18型E6、p53、hWAPL蛋白的表达情况.根据人乳头瘤病毒(HPV)感染情况,206例患者中合并HPV感染117例,未合并HPV感染89例,比较合并与未合并HPV感染宫颈癌患者p53、hWAPL蛋白表达情况,探讨HPV感染与p53、hWAPL蛋白阳性表达的相关性.结果 HPV16/18型E6、p53、hWAPL蛋白在正常宫颈组织、CINⅠ组织、CINⅡ～Ⅲ组织和宫颈癌组织中阳性表达率和阳性表达强度逐渐升高,正常宫颈组织﹤CINⅠ组织﹤CINⅡ～Ⅲ组织﹤宫颈癌组织(P﹤0.01).合并HPV感染患者p53、hWAPL蛋白的阳性表达率均明显高于未合并HPV感染患者(P﹤0.05).Spearmen相关性分析结果显示,宫颈组织中HPV16/18型E6蛋白的阳性表达与p53、hWAPL蛋白的阳性表达均呈正相关(r=0.635、0.701,P﹤0.01),宫颈组织中p53蛋白的阳性表达与hWAPL蛋白的阳性表达呈正相关(r=0.763,P=0.000).结论 合并HPV感染的宫颈癌患者宫颈癌组织中p53?hWAPL的阳性表达率和表达强度均较高,HPV16/18型E6蛋白的阳性表达与p53?hWAPL蛋白的阳性表达均呈正相关.     

多基因联合检测在判断膀胱癌预后价值中的意义

  目的  探讨膀胱癌低级别与高级别两条通路在发生发展过程中的分子变化规律。   方法  应用PCR或低变性温度共扩增PCR(COLD-PCR)与Sanger直接测序法检测88例膀胱癌及10例对照组织中fgfr3、p53与h-ras基因突变状况, 以及MRP-1/CD9 mRNA表达水平及各基因与肿瘤复发之间的关系。Logistic回归及相关性分析比较各基因在肿瘤复发中的意义及相互关系。   结果  癌组织中p53突变率随病理分期及分级的增加而增加, MT-p53患者复发率高于WT-p53;fgfr3突变率则与之相反; 低级别病理分期及分级膀胱癌以MT-fgfr3/WT-p53基因型为主, 高级别病理分期及分级膀胱癌以WT-fgfr3/MT-p53基因型为主。h-ras突变率为11.4%(10/88), 主要分布于低级别病理分期及分级膀胱癌中。MRP-1/CD9 mRNA表达随病理分期及分级的增高而降低, 其表达与p53突变率呈负相关, 与fgfr3突变率呈正相关。在膀胱癌患者中WT-fgfr3复发危险为MT-fgfr3的3.88倍, MT-p53复发危险为WT-p53的4.53倍。   结论  低级别病理分期及分级膀胱癌发生发展中以fgfr3及h-ras基因突变为主, 高级别病理分期及分级肿瘤以p53基因突变、MRP-1/CD9 mRNA表达降低为主。fgfr3与p53突变是预测膀胱癌复发的有力指标, 在膀胱癌发生发展中分别代表不同的遗传学通路, 但低级别与高级别两通路有互相重叠。      

四种基因在单发和多发性膀胱癌组织中的表达及意义

目的探讨p16、p21、p53和上皮细胞膜抗原(EMA)在单发性和多发性膀胱癌组织中的表达及意义。方法收集临床正常、单发和多发性膀胱癌标本,通过免疫组化法检测膀胱癌组织中相关基因的蛋白表达和定位分布。结果与正常膀胱黏膜上皮相比,p16和p53蛋白定位于细胞核,随着膀胱癌恶性程度的升高和侵袭程度的增加,p16蛋白表达明显下降,而p53表达明显升高(P<0.05)。p21蛋白定位于细胞膜,高分化膀胱癌的p21蛋白表达低于低分化膀胱癌(P<0.05);多发性膀胱癌表达阳性率明显高于单发性(P<0.05)。EMA主要表达于细胞浆,随着肿瘤分级和(或)分期的增加,阳性细胞数逐渐减少(P<0.05),在单发和多发性膀胱癌中的表达差异有统计学意义(P<0.05)。结论 p16、p53、p21和EMA在膀胱癌组织中不同水平的表达与膀胱癌的分级/分期密切相关,对膀胱癌相关基因的检测有助于膀胱癌的临床诊断、预后判断和治疗方法的选择。     

动脉化疗栓塞对膀胱癌p53表达的影响及临床意义

目的探讨术前动脉化疗栓塞对膀胱癌组织p53蛋白表达的影响及临床意义。方法对50例化疗栓塞前后的膀胱癌肿瘤组织,应用免疫组织化学方法测定p53蛋白的表达,并分析p53蛋白与膀胱癌病理分级、临床分期以及预后的关系。结果化疗栓塞前高分级、浸润性膀胱癌p53蛋白阳性表达率高于低分级、非浸润性膀胱癌,差异均有统计学意义(P<0.05);化疗栓塞后p53降低程度随着肿瘤的病理分级、临床分期的升高而增加,化疗栓塞前后p53中高度阳性表达率分别为64.0%、30.0%,差异有统计学意义(P<0.01);化疗栓塞前后高分级和浸润性膀胱癌组织中p53蛋白中高度阳性表达水平差异均有统计学意义(P<0.01)。经随访19.8月,总生存率为88.0%,复发率为18.0%(9/50),术后生存率与p53蛋白阳性表达强度间差异在化疗栓塞前无统计学意义(P>0.05),但在化疗栓塞后有统计学意义(P<0.05),而复发率与化疗栓塞前后p53蛋白阳性表达强度间差异均有统计学意义(P<0.05)。结论 p53表达可作为膀胱癌恶性程度判断的预后估计的指标,术前动脉化疗栓塞可以明显降低膀胱癌p53表达,调节膀胱癌的分化程度,降低复发率,提高生存率。     

HPV16E6蛋白及抑癌基因p53在口腔癌中的表达研究

目的 研究HPV16E6蛋白及抑癌基因p53在口腔癌中的表达.方法 回顾性分析100例口腔癌患者的临床资料和病理切片,采用免疫组织化学方法检测口腔癌组织中p53和HPV16E6蛋白的阳性表达情况,分析其与患者临床分期和病理分级的关系.结果 男性口腔癌患者的p53阳性表达率低于女性患者,HPV16E6阳性表达率高于女性患者;年龄﹥50岁口腔癌患者的p53阳性表达率高于年龄≤50岁的患者,HPV16E6阳性表达率低于年龄≤50岁的患者,但差异均无统计学意义(P﹥0.05).口腔癌患者的组织切片显示,p53阳性表达细胞较少,而HPV16E6阳性表达细胞较多.随着患者临床分期的升高(Ⅰ～Ⅳ期),p53阳性表达率呈下降趋势,HPV16E6阳性表达率呈上升趋势,Ⅱ、Ⅲ、Ⅳ期患者与Ⅰ期患者的p53和HPV16E6阳性表达率比较,差异均有统计学意义(P﹤0.05);随着患者病理分级的升高(Ⅰ～Ⅲ级),p53阳性表达率呈下降趋势,HPV16E6阳性表达率呈上升趋势,Ⅱ、Ⅲ级患者与Ⅰ级患者的p53和HPV16E6阳性表达率比较,差异均有统计学意义(P﹤0.05).结论口腔癌患者的p53阳性表达率随患者病理分级与临床分期的升高而降低,HPV16E6阳性表达率随患者病理分级与临床分期的升高而升高,p53阳性表达率的降低和HPV16E6阳性表达率的升高可能与口腔癌的发生和发展有关.     

Significance of HPV Infection and Genic Mutation of APC and K-ras in Patients with Rectal Cancer

Background: Significance of HPV infection and genic mutation of APC and K-ras in rectal cancer has beeninvestigated but not clarified. The objective of our study was to investigate these parameters in patients with rectalcancer to analyze correlations with biological behaviour, to determine relationships among the three, and alsoto demonstrate survival prognosis effects. Methods: From December 2007 to September 2008, 75 rectal cancercases confirmed by histopathology in the Tumor Hospital of Xinjiang Medical University were enrolled. Thecontrol group consisted of normal rectal mucous membrane taken simultaneously, a least 10 cm distant from thecarcinoma fringe. HPV DNA, the MCR of APC and exon-1 of K-ras were detected by PCR and PCR-SSCP. Allresults were analyzed in relation to clinical pathological material, using chi-square and correlation analysis viaSPSS.13 and Fisher’s Exact Probability via STATA. 9.0. All 75 patients were followed up for survival analysisusing Kaplan-Meier and Log-rank tests. Results: 55 out of 75 cases demonstrated gene HPV L1 while it wasnotdetected in normal rectal mucosa tissue. HPV infection was correlated with age and lymphatic metastasis(P<0.05) but not other characteristics, such as ethnicity, tumor size, histological type, tumor type, Duke’s stageand infiltration depth. Some 43 cases exhibited APC genic mutation (57.3%) and 34 K-ras genic mutation(45.3%). APC genic mutation was correlated with gender( P<0.05), but not age, histological type, infiltrationdepth, lymphatic metastasis and Duke’s stage. In 55 cases of rectal cancer with HPV infection, there were 31cases with genic mutation of APC (56.4%) and 24 with genic mutation of K-ras (43.6%). For the 20 cases ofrectal cancer with non-HPV infection, the figures were 12 cases (60%) and 10 (50.0%), respectively, with nosignificant relation. Survival analysis showed no statistical significance for K-ras genic mutation, APC genicmutation or HPV infection (P>0.05). However, the survival time of the patients with HPV infection was a littleshorter than in cases without HPV infection. Conclusions: Our results suggest that HPV infection might be animportant factor to bring about malignant phenotype of rectal cancer and influence prognosis. Genic mutationof APC and K-ras might be common early molecular events of rectal cancer, but without prognostic effects onmedium-term or early stage patients with rectal cancer.     

Expression of RB and p53 proteins in HPV-positive and HPV-negative cervical carcinoma cell lines.

Mutations within the tumor suppressor genes Rb-1 and p53 are commonly found in many human malignancies, and loss of wild-type function of both p53 and RB appear to be important events in the development of these malignancies. Interference with normal RB and p53 function in the cell has apparently also been exploited by the oncogenic genital human papillomaviruses (HPVs), which encode transforming proteins capable of binding cellular RB and p53 proteins. We have investigated the expression of RB and p53 in a series of eight cervical carcinoma cell lines, six of which contain HPV sequences and two of which have arisen apparently independently of HPV infection. In the six HPV-positive lines, no evidence of abnormal RB or p53 protein could be detected. However, there was evidence for abnormal RB and p53 in the two HPV-negative lines. These data are consistent with the hypothesis that loss of wild-type RB and p53 function is necessary for tumor development and that such loss can occur either by mutation within the cellular gene or by expression of viral proteins capable of complexing wild-type cellular proteins.     

人乳头瘤病毒感染和p53基因突变与宫颈癌的关系

目的：探讨人乳头瘤病毒１６ 和１８ 型及抑癌基因ｐ５３ 突变对宫颈的致癌作用以及 Ｈ Ｐ Ｖ 感染与ｐ５３ 基因突变的相关性。方法：采用聚合酶链反应（ Ｐ Ｃ Ｒ） 技术和限制性酶切片段多态性分析（ Ｒ Ｆ Ｌ Ｐ） 技术对３４ 例原发性宫颈癌组织及３０ 例正常宫颈组织 Ｈ Ｐ Ｖ１６ ,１８ 型 Ｄ Ｎ Ａ 及抑癌基因ｐ５３ 的突变进行了检测。结果： Ｈ Ｐ Ｖ１６ ,１８ Ｄ Ｎ Ａ 在宫颈癌的总阳性率为６４７ ％ （２２／３４） ,正常宫颈组织只有６７ ％ 阳性,８例宫颈癌组织出现ｐ５３ 基因第６ 外显子突变,其中２ 例为 Ｈ Ｐ Ｖ１６ Ｄ Ｎ Ａ 阳性、１ 例 Ｈ Ｐ Ｖ１８ Ｄ Ｎ Ａ 阳性。结论：宫颈癌的发病与 Ｈ Ｐ Ｖ 感染及ｐ５３ 基因突变有关,宫颈癌组织中ｐ５３ 基因突变与 Ｈ Ｐ Ｖ 感染无关。     

HPV16,HPV18感染及p53,p21基因突变与胃癌预后研究

目的：了解胃癌组织中ＨＰＶ１６、ＨＰＶ１７８的感染及Ｐ５３、Ｐ２１基因突变是否存在协同致癌作用及其与胃癌患者的预后的关系。方法：采用聚合酶链（ＰＣＲ）技术,检测６４例胃癌组织标本中人乳头瘤病毒１６、１８型感染,并采用免疫组化Ｓ－Ｐ法对胃癌Ｐ５３、Ｐ２１基因突变进行检测。结果：ＨＰＶ１６阳性率为４３．７５％,ＨＰＶ１８阴性;Ｐ５３基因突变率为４６．８７％;Ｐ２１阳性表达为５３．１２％。三项同时发生率     

Frequent occurrence of p53 gene mutations in uterine cancers at advanced clinical stage and with aggressive histological phenotypes.

The clinical and pathological significance of mutation of the p53 tumor-suppressor gene was examined in 108 cases of primary uterine cancers using single-strand conformation polymorphism and direct DNA sequencing analyses. Mutation of the p53 gene was detected in 19 (31%) of 62 cases of cancer of the uterine corpus and was more frequent in groups at an advanced clinical stage and/or with aggressive histology. Among four adenocarcinomas arising in the lowest portion of the uterine corpus, three showed integration of human papillomavirus (HPV) types 16 and/or 18 DNA, and two of them also showed p53 mutation. In cancer of the uterine cervix, p53 mutations were rare; 7% (3/46) in total, 3% (1/30) of cases with integration of HPV types 16 and/or 18 DNA and 13% (2/16) of cases without HPV DNA integration. Three mutations were detected among two cases at clinical stage IV and two cases of undifferentiated cervical carcinoma. Immunohistochemically, all five cases of uterine cancer which showed diffuse (> 50% of cancer cells) nuclear staining of p53 protein also carried the p53 mutation. Therefore, p53 alterations were suggested to be involved in the development of uterine cancers showing aggressive biological behavior. Although a high incidence of HPV DNA integration and a low incidence of p53 mutation were confirmed in cancer of the uterine cervix, there was no inverse association between integration of HPV types 16 and/or 18 DNA and p53 mutation.     

Frequent Occurrence of p53 Gene Mutations in Uterine Cancers at Advanced Clinical Stage and with Aggressive Histological Phenotypes

The clinical and pathological significance of mutation of the p53 tumor-suppressor gene was examined in 108 cases of primary uterine cancers using single-strand conformation polymorphism and direct DNA sequencing analyses. Mutation of the p53 gene was detected in 19 (31%) of 62 cases of cancer of the uterine corpus and was more frequent in groups at an advanced clinical stage and/or with aggressive histology. Among four adenocarcinomas arising in the lowest portion of the uterine corpus, three showed integration of human papillomavirus (HPV) types 16 and/or 18 DNA, and two of them also showed p53 mutation. In cancer of the uterine cervix, p53 mutations were rare; 1% (3/46) in total, 3% (1/30) of cases with integration of HPV types 16 and/or 18 DNA and 13% (2/16) of cases without HPV DNA integration. Three mutations were detected among two cases at clinical stage IV and two cases of undifferentiated cervical carcinoma. Immunohistochemically, all five cases of uterine cancer which showed diffuse (>50% of cancer cells) nuclear staining of p53 protein also carried the p53 mutation. Therefore, p53 alterations were suggested to be involved in the development of uterine cancers showing aggressive biological behavior. Although a high incidence of HPV DNA integration and a low incidence of pS3 mutation were confirmed in cancer of the uterine cervix, there was no inverse association between integration of HPV types 16 and/or 18 DNA and p53 mutation.     

The role of p53 inactivation in human cervical cell carcinoma development.

We investigated the association between human papillomavirus (HPV) infection and p53 gene mutation in 47 primary uterine cervical cancers. HPV DNA sequences were present in 43 cancers (91.5%), and one of these cancers contained a p53 gene mutation. In addition, one of the remaining four HPV-negative cancers also contained a p53 gene mutation. As a result, p53 inactivation corresponded to the development of 44 of the primary uterine cervical cancers studied (93.6%). We obtained both primary and recurrent tumours from four cases. In two of these cases, the HPV genomes that were present in an episomal state in the primary tumours were observed to have disappeared in the recurrent tumours. One of these recurrent tumours also contained a p53 gene mutation, which suggested the possibility that p53 inactivation was required in order to maintain the aggressive behaviour in this cancer either by an HPV infection or by a p53 gene mutation. No MDM2 gene amplification was observed in the tumours that carried neither HPV DNAs nor p53 gene mutations.     

The carcinogenic role of oncogenic HPV and p53 gene mutation in cervical adenocarcinomas

Thirty tumors were collected from our archive of cervical adenocarcinomas. They were examined with respect to the content of oncogenic HPV and presence of mutations in the p53 gene exons 5 through 8. Furthermore, available clinical information on the cases was reviewed. For the detection of p53 gene and presence of oncogenic HPV, PCR followed by direct sequence analysis of the amplified DNA was employed. Seventeen tumors were identified as HPV-positive, comprising both HPV types 18 and 16. Six cases showed a p53 gene mutation, of which five were of the missence and one of the silent type. No statistical correlation between the occurrence of oncogenic HPV and presence of p53 gene mutation (p=0.67) was recorded. Among the tumors with p53 gene mutation, three were HPV-positive and three were HPV-negative. The determination of p53 gene mutations was not related to clinical findings such as the stage of the tumor or presence of metastases of the lymph nodes. However, p53 gene mutations were somewhat more prevalent in low differentiated tumors (p<0.02). The results indicate that oncogenic HPV and p53 gene mutations have independent carcinogenic roles in cervical adenocarcinomas.     

Human papilloma virus infection and overexpression of p53 protein in bilharzial bladder cancer.

AIMS AND BACKGROUND: An association between human papilloma virus (HPV) and bladder cancer has been reported. However, the role of HPV in bilharzial bladder cancer and its prevalence have not yet been clarified. STUDY DESIGN: We investigated 50 cases for HPV types 16/18 by in situ hybridization. Also, p53 protein expression by immunohistochemistry was evaluated in 41 of the 50 cases, with correlation of these factors to clinicopathologic parameters and tumor relapse after primary treatment. RESULTS: HPV was detected in 46% of Egyptian bladder carcinomas (23/50 cases). Positivity was 47.8% for squamous cell carcinoma and 36.4% for transitional cell carcinoma. There was a possible viral-bilharzial association as 52.8% of Bilharzial cases, whereas only 12.5% of non-Bilharzial cases were HPV positive (P <0.05). P53 protein was found in 19/41 (46.3%) cases. There was a concordance between HPV and p53 in 58.5% of cases. Neither factor was related to tumor recurrence after primary treatment. CONCLUSIONS: HPV may thus be implicated in the etiology of bilharzial bladder cancer, but a definite causal relationship remains to be demonstrated. HPV together with p53 alterations work in synergy to accelerate the carcinogenic process, as there was concordance in the results of both parameters in 24/41 (58.5%) cases.     

HPV感染与p53蛋白及P-糖蛋白表达在非小细胞肺癌中的关系及其临床意义

目的:探讨人乳头瘤病毒(humanpapillomavirus,HPV)感染在非小细胞肺癌(nonsmallcelllungcancer,NSCLC)发生中的病因学意义及其与p53蛋白和P糖蛋白(Pgp)表达之间的相关性。方法:应用PCR、免疫组化方法分别检测76例NSCLC组织中HPVDNA及其E6、E7原癌蛋白、p53蛋白和Pgp的表达情况。结果:NSCLC中HPVDNA及其E6、E7原癌蛋白的检出率分别为40.8%(31/76)、43.4%(33/76),2种检测方法的符合率为78.9%(60/76);p53蛋白和Pgp的阳性率分别为63.2%(48/76)、59.2%(45/76),且HPV感染阳性组中p53蛋白的表达率为80.6%(25/31),显著高于阴性组51.1%(23/45)(P<0.05);p53蛋白表达阳性组中Pgp的表达率为68.8%(33/48),显著高于阴性组42.9%(12/28)(P<0.05);而HPV感染阳性组与阴性组间Pgp的表达无显著性差异(P>0.05)。HPV感染与高、中分化程度的NSCLC及吸烟有关。结论:HPV感染可能是NSCLC发生的另一重要病因学因素,且HPV感染可能导致p53基因突变,后者可能促进肺癌耐药性的增加。