人乳头状瘤病毒（HPV）和P53蛋白在尖锐湿疣与阴茎癌中的表达

目的：探讨ＨＰＶ及Ｐ５３蛋白在尖锐湿疣和阴茎鳞癌中的表达情况。方法：在常两全时确定诊断后，用ＳＰ免疫组化法显示内的ＨＰＶ抗原和Ｐ５３蛋白。结果：尖锐湿疣２１例，ＨＰＶ标记均阳性，Ｐ５３蛋白标记５例见低度表达。阴茎鳞癌１９例，ＨＰＶ标记阳性２例，Ｐ５３蛋白标记２例见过度表达（阳性率６３％），其中６例强阳性。结论：尖锐湿疣与ＨＰＶ感染有关，少数见Ｐ５３蛋白低度表达；而阴茎鳞癌中常见Ｐ５３蛋白过度表达，     

高危性人乳头瘤病毒与抑癌基因P53在膀胱癌中的表达

用ＰＣＲ法检测５２例膀胱癌组织中人高危性乳头瘤病毒（ＨＰＶ）ＤＮＡ，同时用免疫组化方法检测其Ｐ５３蛋白的过度表达，发现２８例（５３．８４％）ＨＰＶＤＮＡ阳性，１９例（３６．５４％）肿瘤细胞核Ｐ５３染色阳性，二者同时阳性者３例（５．７７％）。ＨＰＶＤＮＡ阳性者多见于高分化、非侵袭性肿瘤中，相反Ｐ５３蛋白阳性则主要表现在低分化、侵袭性肿瘤中。ＨＰＶＤＮＡ和Ｐ５３的表达呈显著性负相关（ｒ＝－０．５７６９）。结果提示：ＨＰＶ感染或Ｐ５３的过度表达与膀胱肿瘤的生物学行为有关，并可将其作为膀胱肿瘤的预后评价指标。     

阴茎癌组织中人乳头瘤病毒DNA的原位杂交研究

为了研究人乳头瘤病毒与阴茎癌的关系，应用地高辛标记的ＨＰＶ６、ＨＰＶ１１、ＨＰＶ１６和ＨＰＶ１８ＤＮＡ探针分别对４６例阴茎癌组织进行原位杂交检测ＨＰＶＤＮＡ。结果显示：ＨＰＶＤＮＡ阳性２２例，其中ＨＰＶ１６ＤＮＡ阳性２０例，ＨＰＶ１８ＤＮＡ阳性４例，在２例转移癌和癌旁不典型增生组织中检测到了ＨＰＶ１６ＮＤＡ，未见ＨＰＶ６ＤＮＡ和ＨＰＶ１１ＤＮＡ阳性，ＨＰＶＤＮＡ位于癌细胞核中。结果表明原位杂交可以用来研究阴茎癌组织中ＨＰＶ的存在及分型，同时也证实了阴茎癌的发生和ＨＰＶ１６及ＨＰＶ１８感染有密切关系     

P53,Ras基因突变及HPV感染与膀胱癌的关系

应用分子生物学方法检测３２例膀胱移行上皮癌中Ｐ５３、Ｋ－ｒａｓ、ＨＰＶ基因，发现有３４．４％的膀胱癌Ｐ５３基因突变，２１．９％膀胱癌Ｋ－ｒａｓ基因突变，６．３％膀胱癌ＨＰＶ阳性。说明膀胱移行上皮癌的发生与Ｐ５３、Ｒａｓ基因突变及ＨＰＶ感染有关。膀胱癌的发生是多种基因的变化通过多种途径引起的。     

HIV阳性病人中与人乳头状瘤病毒有关的阴茎鳞状细胞癌

阴茎鳞状细胞癌在欧美相对不常见 ,但在一些亚洲、非洲及拉丁美洲地区却很常见。已知的一些有关的发病危险因素包括没有新生儿包皮环切及性传播疾病。人乳头状瘤病毒 (ＨＰＶ)是感染皮肤及粘膜的ＤＮＡ病毒 ,已知的九十多型ＨＰＶ中有近四十型ＨＰＶ可以感染泌尿生殖道。作者报道了 2例ＨＩＶ感染病人发生的阴茎鳞状细胞癌 ,组织相呈高分化、浸润性 ,可见从良性尖锐湿疣到浸润性鳞癌的过程 ;除组织学上有ＨＰＶ感染的证据而外 ,通过多聚酶链式反应 (ＰＣＲ)均测得ＨＰＶＤＮＡ。有报道认为ＨＰＶＤＮＡ10 0 %出现在高分化阴茎癌中 ,但ＨＰＶ…     

人乳头瘤病毒DNA相关序列与p53基因突变对大肠癌生物学行为的影响50例报告

目的探讨人乳头瘤病毒（ＨＰＶ）ＤＮＡ相关序列与ｐ５３基因突变及ｐ５３蛋白表达的关系及其对大肠癌生物学行为的影响。方法采用ＰＣＲ方法检测大肠癌及癌旁组织、肝转移灶中ＨＰＶＤＮＡ相关序列。并应用ＰＣＲＳＳＣＰ及免疫组化技术分别检测ｐ５３基因突变及ｐ５３蛋白表达。结果在５０例大肠癌中,检出ＨＰＶ１６、１８ＤＮＡ相关序列２６例（５２０％）,其中ＨＰＶ１６ＤＮＡ４例（８０％）,ＨＰＶ１８ＤＮＡ２２例（４４０％）。ｐ５３基因突变率为５６０％。ｐ５３蛋白表达阳性率为４２０％。ＨＰＶＤＮＡ相关序列与ｐ５３基因突变及ｐ５３蛋白表达呈正比关系。结论ＨＰＶＤＮＡ相关序列可促进细胞转化、致ｐ５３基因突变、抑制细胞的凋亡,与大肠癌的发生发展有密切关系。     

聚合酶链反应和核酸杂交在检测阴茎癌人乳头状瘤病毒中的作用

人乳头状瘤病毒（ＨＰＶ）为一种潜在的癌基因，可能为多种泌尿生殖道肿瘤的致病因子。作者用高敏感的聚合酶链反应（ＰＣＲ）结合和核酸杂交方法，检测２８例阴茎癌组织中的ＨＰＶ１６，１８型病毒，结果表明：阴茎癌组织中ＨＰＶ１６的阳性检出率为５０％（１４／２８），ＨＰＶ１８的阳性检出率为１０．６％（３／２８）。提示ＨＰＶ１６感染在阴茎癌的发生过程中可能具有重要作用，并且与患者吸烟有关     

肿瘤病毒对P53和Rb的影响

肿瘤病毒对Ｐ５３和Ｒｂ的影响韩见知，章咏裳，李家贵肿瘤病毒与人类癌症的发生和发展有密切的关系。主要的肿瘤病毒有人类乳头状病毒（ＨＰＶ），腺病毒和猿病毒４０（ＳＶ４０）。研究还发现肿瘤病毒及其ＤＮＡ蛋白的表达水平与泌尿生殖系癌症如阴茎癌、尿道癌、膀胱癌...     

人乳头瘤病毒DNA相关序列与p53基因突变对大肠癌生物学行为 …

目的 探讨人乳头瘤病毒ＤＮＡ相关序列与ｐ５３基因突变及Ｐ５３蛋白表达的关系,及其对大肠癌生物学行为的影响。方法 采用ＰＣＲ方法检测大肠癌及癌旁组织,肝转移灶中ＨＰＶＤＮＡ相关序列。并应用ＰＣＲ－ＳＳＣＰ及免疫组化技术分别检测Ｐ５３基因突变及Ｐ５３蛋白表达。     

骨肿瘤组织P^53蛋白表达及临床意义的研究

应用抗Ｐ＾５３单克隆抗体免疫组织化学方法，检测了６７例肿瘤组织标本Ｐ＾５３蛋白的表达。结果显示：２０你骨肉瘤组织中有９例ＰＯ＾５３蛋白表达阳性，而４７例骨软骨瘤，骨巨细胞瘤均呈阴性反应。Ｐ＾５３蛋白表达与患者的性别，传统的骨肉瘤病理分型，大小，临床分期无明显相关。Ｐ＾５３蛋白表达阳性的骨肉     

Human papillomavirus and p53 protein immunoreactivity in condylomata acuminatum and squamous cell carcinoma of penis

Aim: To determine the immunoreactive pattern of human papillomavirus (HPV) antigen and p53 protein in condylomata acuminatum (CA) and squamous cell carcinoma (SCC) of penis. Methods: Immunohistochemistry for HPV and p53 were performed in 40 specimens of formalin fixed, paraffin embedded tissues using a polyclonal (rabbit) antibody against HPV and a monoclonal (mouse) antibody against human p53 protein. Twenty one cases of CA and nineteen cases of SCC were examined. Results: HPV antigen was detected in all 21 CA and 2 penile SCC. p53 protein overexpression was observed in 12 of 19 (63%) SCC in which 6 cases were strong positive. Five of 21 CA (24%) showed low-grade p53 protein overexpression. Conclusion: CA is related to HPV infection and some cases show p53 protein low-grade overexpression. In contrast, p53 protein overexpression is common in penile SCC, which is seldom related to HPV infection.     

Human Papillomavirus and Overexpression of P16INK4a in Nonmelanoma Skin Cancer

BACKGROUND: P16INK4a overexpression has been identified as a specific biomarker in high-risk human papillomavirus (HPV)-infected cervical (pre)cancer lesions. OBJECTIVE: To evaluate the overexpression of this cyclin-dependent kinase inhibitor in skin tumors depending on HPV infections, we analyzed normal skin, benign skin disease, and skin cancer specimens. METHODS: Biopsies of 23 patients with normal histology (3), psoriasis (2), verrucae vulgaris (2), actinic keratoses (5), squamous cell carcinoma (SCC) in situ (3), Bowen's carcinoma (1), and SCC (7) were analyzed. Specimens of 23 patients were immunostained using the monoclonal antibody E6H4 specific for p16INK4a. HPV status was assessed by a polymerase chain reaction (PCR) system to detect all currently known HPV types. MY (MY09/MY11 and MYN9/MYN10)-, CP (CP65/CP70 and CP66/CP69)-nested PCR, and three single PCR methods CN1, CN3, and CN4 were used in a first step, and HPV typing was performed by restriction fragment length polymorphism analysis. Only beta-globin-positive patients were included in this study. RESULTS: HPV DNA was detected in all actinic keratoses, SCC in situ, Bowen's carcinoma, and SCC, in 50% (one of two) of verrucae vulgaris, in 66% (two of three) of normal skin, and in none of two psoriasis. P16INK4a expression was not detected in normal skin, psoriasis, and verrucae vulgares. Overexpression of p16INK4a was detected in a subset of dysplastic cells (10% to 80%) of all skin (pre)cancer lesions such as actinic keratoses, SCC in situ, Bowen's carcinoma, and SCC infected with HPV independent of sun exposure. CONCLUSION: P16INK4a appears to be overexpressed in a portion of dysplastic cells from actinic keratoses and SCC. Further studies to examine the association of HPV infection and the overexpression of p16INK4a are warranted.     

The expression of key cell cycle markers and presence of human papillomavirus in squamous cell carcinoma of the tonsil

BACKGROUND: Chemical carcinogens induce squamous cell carcinoma (SCC) of the head and neck by targeting the p53 and the retinoblastoma (pRb) pathways. Human papillomavirus (HPV) might have an etiologic role in these cancers at particular sites. Few studies have compared cell cycle protein expression in HPV-positive and HPV-negative tumors in this region. METHODS: Fifty tonsil SCCs were analyzed for HPV by PCR and for expression of cell cycle proteins (p53, pRb, p16(INK4A), p21(CIP1/WAF1), p27(KIP1), and cyclinD1) by immunohistochemistry. RESULTS: HPV was present in 42%; almost all were type 16. There were statistical associations between HPV positivity and reduced expression of pRb and cyclinD1, overexpression of p16, and younger patient age. Tumor with down-regulated p27 tended to have down-regulated pRb and p21. CONCLUSIONS: HPV-positive tonsil SCCs have distinct molecular pathways. Their association with younger patient age suggests that they are biologically distinct from HPV-negative tumors.     

乳腺癌患者高危型人乳头状瘤病毒感染、p53蛋白表达及淋巴结转移分析

目的分析乳腺癌患者高危型人乳头状瘤病毒（HPV）感染、p53蛋白表达和淋巴结转移率。 方法选取2016年5月至2018年5月于西北妇女儿童医院治疗的乳腺癌患者共90例作为观察组,选取同期于本院治疗乳腺增生患者90例作为对照组。对癌组织行HPV基因分型和p53蛋白检测,增生组织行HPV基因分型。观察入组患者高危型HPV感染率,分析乳腺癌患者肿瘤大小、TNM分期、淋巴结转移率与p53蛋白表达等。 结果观察组患者中共60例发生高危型HPV感染,对照组中共36例发生高危型HPV感染,观察组患者中HPV16、18基因型感染率分别为21.11%（19/90）和22.22%（20/90）,均高于对照组[2.22%（2/90）和2.22%（2/90）],差异均有统计学意义（χ² = 7.108、P = 0.001,χ² = 8.063、P = 0.001）。观察组HPV阳性患者淋巴结转移率为93.33%（56/60）,显著高于HPV阴性患者（21/30、70.00%）,差异有统计学意义（χ² = 4.072、P = 0.002）。观察组患者中p53蛋白阳性者39例（39/90、43.33%）,其中肿瘤大小≤ 2 cm者27例（27/39、69.23%）、TNM分期Ⅰ期、Ⅱ期、Ⅲ期和Ⅳ期分别占15.38%（6/39）、30.77%（12/39）、35.90%（14/39）和17.95%（7/39）,淋巴结转移率为82.05%（32/39）;p53蛋白阴性患者51例（51/90,56.67%）,肿瘤大小≤ 2 cm者35例（35/51、68.63%）、TNM分期Ⅰ期、Ⅱ期、Ⅲ期和Ⅳ期分别占7.84%（4/51）、19.61%（10/51）、49.02%（25/51）和23.53%（12/51）,淋巴结转移率为86.27%（44/51）,p53蛋白阴性组与p53蛋白阳性组患者肿瘤大小、TNM分期及淋巴结转移率差异均无统计学意义（χ² = 0.682、P = 0.462,χ² = 0.491、P = 0.507,χ² = 0.572、P = 0.461）。 结论检测乳腺癌患者高危型人乳头状瘤病毒感染、p53蛋白表达及淋巴结转移率有助于对乳腺癌的诊疗;p53蛋白阳性率下降可能促进HPV感染相关肿瘤的发生和发展。     

Prevalence of human papillomavirus infection in the urinary tract of men with urethritis

Objectives: To investigate the prevalence of human papillomavirus (HPV) in the genital and urinary tract of men with urethritis. Methods: Cell samples were collected from the penis, urethra and urine of 142 men with urethritis. A HPV test was performed on the samples using the modified GP5+/6+ polymerase chain reaction method, and the HPV genotype was determined using a HPV GenoArray test. Results: Out of 142 urethritis patients, HPV was detected in 48% (68 cases), and high‐risk HPV was found in 32% (46 cases) of patients, on their penis or in the urinary tract (urethra or urine). HPV was detected in 31% in the penis, 20% in the urethra and 24% in the urine, while high‐risk HPV was identified in 23% in the penis, 12% in the urethra and 11% in the urine. Among the HPV‐positive men, 66% had HPV infection in the urinary tract where the most common HPV types were HPV6, HPV16, HPV18 and HPV58. Single HPV‐type infection was more frequently found in the urinary tract (89%) than in the penis (65%) (P < 0.05). Conclusions: Similar to the penis, the urinary tract represents a common HPV infection site in men with urethritis.     

Presence of human papillomavirus DNA and abnormal p53 protein accumulation in lung carcinoma.

BACKGROUND: In some carcinomas inactivation of the tumour suppressor gene product p53, either by point mutation or indirectly by the human papillomavirus (HPV), has been suggested as two alternative routes to malignant transformation. To test this hypothesis in lung tumours, 43 lung carcinomas were analysed by in situ hybridisation and polymerase chain reaction (PCR) for the presence of HPV DNA, and the results were compared with p53 protein immunohistochemical analysis. METHODS: The presence of HPV DNA in lung carcinoma was detected by nucleic acid in situ hybridisation for HPV types 6, 11, 16, 18, 31, and 33 using nonradioactively labelled DNA probes. Polymerase chain reaction (PCR) analysis was performed on all cases showing positive HPV DNA labelling by in situ hybridisation and in an additional 13 negative cases. Abnormal nuclear accumulation of the p53 protein was revealed by immunohistochemistry using the avidin-biotin-peroxidase complex method and a CM-1 polyclonal anti-human p53 antibody and a monoclonal mutation-specific Pab 240 p53 antibody. RESULTS: HPV DNA was found by in situ hybridisation in 13 lung carcinomas (30%). In all these cases subtype-specific HPV DNA could also be detected by PCR. Abnormal p53 protein accumulation was seen in 21 of the 43 carcinomas (49%), of which 18 were HPV negative. Twelve (57%) of the CM-1 positive cases were also positive for the mutation-specific antibody Pab 240. There was an obvious inverse relationship between the presence of papilloma viral DNA and abnormal p53 protein accumulation. CONCLUSIONS: p53 plays an important part in the development of lung carcinomas and, in some cases, HPV may contribute to it by binding and inactivating the p53 protein.     

Detection of human papillomavirus DNA and expression of p16, Rb, and p53 proteins in small cell carcinomas of the uterine cervix

Human papillomavirus (HPV) has been implicated as an etiologic agent for the development of primary small cell carcinoma of the uterine cervix, a rare but highly aggressive malignancy. It has been shown that the HPV E6 and E7 oncoproteins are able to inactivate the tumor suppressor functions of p53 and Rb. In squamous cell carcinoma and adenocarcinoma of the cervix, HPV infection is also associated with overexpression of p16, a cyclin-dependent kinase inhibitor. In this study, 22 cases of primary small cell carcinoma of the uterine cervix were subjected to broad-spectrum HPV DNA amplification and typing, and immunohistochemically examined for the expression of p16, Rb, and p53 proteins. The results show that HPV DNA was detected in every case (100%), with 18 cases (82%) harboring type 18. The tumor cells exhibited strong nuclear staining for p16 in 20 cases (91%). This was associated with a complete loss of Rb nuclear staining in tumor cells in 16 cases (73%). The p53 protein was essentially undetectable in all cases. In contrast, HPV DNA was not detected in 9 colorectal and 8 urinary bladder small cell carcinomas included in this study for comparison. While similar p16 and Rb expression patterns were observed in these HPV-negative tumors, a different expression pattern for p53 was noted where strong nuclear staining was seen in 8 cases (47%; P = 0.0004 compared with cervical tumors). These observations indicate that different mechanisms are involved in the pathogenesis of small cell carcinomas of the uterine cervix and support the notion that nuclear p16 overexpression serves as an indication of Rb defunctioning in tumor cells, which may or may not result from high-risk HPV infection.     

阴茎癌及其癌旁组织中癌基因ras产物P~(21)蛋白的表达

用免疫量化ABC法检测32例阴茎癌,32例癌旁组织和16例正常阴茎组织的癌基因ras产物P~(21)蛋白。结果28例癌组织,8例癌旁组织中有P~(21)蛋白表达,而16例正常阴茎组织中P~(21)阴性。P~(21)蛋白表达和病理可分级、临床分期呈正相关。癌旁组织P~(21)蛋白表达阳性都显示了早期复发和转移的不良预后。