尖锐湿疣和外阴鳞状细胞癌中hTERT mRNA和survivin的表达及其相互关系

目的:探讨人端粒酶逆转录酶(hTERT)及凋亡抑制基因生存素(survivin)在尖锐湿疣(CA)及外阴鳞状细胞癌(VSCC)组织中的表达及其临床意义。方法:SP免疫组化染色检测48例CA、31例VSCC及13例正常皮肤组织中survivin蛋白表达水平;原位杂交技术检测上述组织中人端粒酶逆转录酶(hTERT)mRNA表达水平。结果:CA组hTERT mRNA表达的阳性率与正常对照组比较差异无显著性,与VSCC组比较差异有显著性;CA组、VSCC组及正常对照组中survivin蛋白表达的阳性率差异均有显著性;VSCC组中hTERT mRNA表达与survivin蛋白表达的阳性率呈明显的正相关(P<0.05)。结论:survivin与CA及VSCC的发生发展密切相关;hTERT可作为鉴别良性和恶性肿瘤的辅助指标,但不能反映良性肿瘤的增殖情况;hTERT与survivin在VSCC中的表达具有一定的协同性。     

皮肤鳞状细胞癌中人乳头瘤病毒的检测

目的:检测皮肤鳞状细胞癌(SCC)皮损中的人乳头瘤病毒(HPV)并探讨其在SCC发病中的作用.方法:用原位杂交(ISH)、聚合酶链反应技术(PCR)检测SCC患者43例,健康者28例标本组织切片中的HPV6、11、16、18、31、33.结果:43例SCC中有2例肢端部位皮损呈HPV DNA阳性,检出类型为HPV16和HPV33.其中1例标本中HPV16和HPV33同时阳性.对照组全部为阴性.结论:HPV16等6种黏膜型HPV可能与肢端以外SCC的发生无相关性,而与肢端部位SCC可能有关联性.     

人乳头瘤病毒与皮肤鳞状细胞癌

皮肤鳞状细胞癌(SCC)病因复杂,人乳头瘤病毒(HPV)感染可能对其恶性演变起一定作用。对二者之间关系进行的研究较多,但结论多不一致,本文就相关研究和病毒致癌的可能机制作一综述。     

外阴鳞状上皮内瘤变皮损中人乳头瘤病毒16、18癌基因整合性研究

目的探讨人乳头瘤病毒(HPV)16、18在外阴鳞状上皮内瘤变(VIN)皮损中的感染和其癌基因在人基因组中的整合情况。方法采用捕获杂交法及PCR技术筛选高危型HPV和HPV16、18DNA阳性VIN标本：经RT-PCR、巢式PCR及DNA杂交研究HPV16、18 DNA阳性VIN标本中的HPV基因转录。结果 32例VIN患者皮损中24例(75%)为高危型HPV阳性,23例为HPV 16阳性,1例为HPV 18阳性。23例HPV 16阳性标本中除1例VIN Ⅱ皮损无HPV转录外,15份标本为游离体型HPV 16基因转录,其余7例VIN Ⅲ标本呈现整合型HPV 16癌基因转录；1例HPV 18阳性VIN Ⅲ标本发现为整合型HPV 18癌基因转录。结论大部分VIN Ⅱ、Ⅲ标本存在HPV 16感染,HPV癌基因的整合多发生于VIN Ⅲ的皮损；推测高危型HPV癌基因在人基因组中的整合与VIN的发生及其向外阴鳞状细胞癌的发展有关。     

外阴鳞状细胞癌中人乳头状瘤病毒感染与基质金属蛋白酶9和金属蛋白酶抑制剂1的关系

目的 探讨人乳头状瘤病毒(HPV)6/11、16/18在外阴鳞状细胞癌(简称外阴鳞癌)组织中的感染情况及与基质金属蛋白酶9(MMP-9)和金属蛋白酶抑制剂1(TIMP-1)蛋白表达的关系.方法 用原位杂交法检测HPV6/11、16/18在26例外阴鳞癌、21例外阴上皮内瘤病变(VIN)及10例外阴正常皮肤组织中的感染情况.同时用免疫组化法检测MMP-9、TIMP-1蛋白的表达.结果 HPV6/11、16/18在外阴鳞癌、VIN中的感染率分别为69.23%(18/26)和38.46%(10/26),42.86%(9/21)和28.57%(6/21),正常对照组没有感染.MMP-9、TIMP-1蛋白在外阴鳞癌、VIN、正常对照组中的阳性表达率分别为92.31%(24/26)和76.92%(20/26),90.48%(19/21)和80.95%(17/21),80.00%(8/10)和50.00%(5/10).HPV6/11的外阴鳞癌组、VIN组与正常对照组比较差异有显著性(P<0.05),HPV16/18的外阴鳞癌组与正常对照组比较差异有显著性.外阴病变各组MMP-9、TIMP-1阳性表达率与正常对照组比较差异均有显著性.在外阴鳞癌中MMP-9蛋白表达较TIMP-1蛋白表达强(P<0.05).MMP-9在有HPV6/11和HPV16/18感染患者中的表达较无感染者强,而TIMP-1蛋白的表达差异无显著性.结论 在外阴鳞癌的发生发展中HPV的感染起一定作用,当MMP-9的表达强于TIMP-1表达时可能是外阴鳞癌侵袭的一个指标,HPV感染可能会进     

阴茎鳞状细胞癌1例

报告1例阴茎鳞癌，患者男，50岁，阴茎龟头菜花样肿块3年，破溃1年，3年半前有尖锐湿疣史，皮损组织人乳头瘤病毒（HPV）6，11型阳性，组织病理，高分化鳞癌（龟头皮损），淋巴结慢性炎症和反应性增生（右腹股沟）。     

皮肤鳞状细胞癌组织中人乳头瘤病毒型别的检测

目的分析皮肤鳞状细胞癌患者感染人乳头瘤病毒(HPV)的现状和分布规律,探讨HPV感染与皮肤鳞状细胞癌发生的关系。方法应用多聚酶链式反应(PCR)技术对300例组织病理学诊断为皮肤鳞状细胞癌的组织标本进行HPV DNA检测,主要检测型别为HPV6、11、16、18、31、33。结果 300例皮肤鳞状细胞癌患者中,HPV阳性188例,HPV感染率为62.67%;男性HPV感染率为66.33%,女性HPV感染率为55.78%,性别差异无统计学意义(P0.05)。高分化(Ⅰ~Ⅱ级)HPV感染率为67.86%,低分化(Ⅲ~Ⅳ级)HPV感染率为47.37%,两组之间差异有统计学意义(P0.01)。头面部、颈部、四肢、躯干以及生殖器和腹股沟部HPV感染率分别为70.23%、65.79%、43.33%、28.00%和68.42%。共检出高危型(HPV16和HPV33)感染51例,低危型(HPV6)感染49例,均为单一型别感染。结论 HPV感染型别检测对皮肤鳞状细胞癌的防治有重要意义。     

外阴硬化萎缩性苔藓与外阴鳞状细胞癌的基因研究

外阴硬化萎缩性苔藓是较为常见的一种慢性皮肤黏膜病变，部分患者可能发展为外阴鳞状细胞癌。近年来的研究发现，外阴硬化萎缩性苔藓可能与多种癌基因、抑癌基因突变及其表达异常存在着密切联系。综述与外阴硬化萎缩性苔藓和外阴鳞状细胞癌相关的十余种癌基因与抑癌基因，分析从外阴硬化萎缩性苔藓发展到外阴鳞状细胞癌的因素。     

巨大型锐湿疣与鳞状细胞癌及癌前病变关系的研究

目的：观察女性生殖道普通尖锐湿疣、巨大型尖锐湿疣、上皮不典型增生及太细胞癌的细胞增殖活性和人类乳头状瘤病毒感染的主要亚型分布，探讨这4种病变之间的内在联系。方法：采用核仁组成区嗜银蛋白染色（AgNOR）、免疫组化染色（SP法）以及原位分子杂交（ISH）和聚合酶链反应（PCR）检测这4种病变中PCNA、P53、C－erbB-2的表达以及HPV6／11和HPV16／18亚型的分布。结果：巨大型尖锐湿疣和上皮不典型增生的AgNOR颗粒面积／核面积比，以及PCNA的阳性指数（PI）和平均吸光度这些反映细胞增生活性的指标上差异无显著性。但与普通尖锐湿疣和鳞状细胞癌两组相比较，其差异有非常显著性（P＜0．01）。在癌基因蛋白P53的表达上，此4组病变之间均有不同。C－erbB-2在鳞状细胞癌组中阳性率较高，而其余3组病变之间阳性率差异无显著性。普通尖锐湿疣感染的HPV亚型主要是低危型的6／11型（16／22例），鳞状细胞癌和上皮不典型增生主要感染的HPV亚型为高危型的16／18型（9／14例和3／6例）。巨大型尖锐湿疣感染的HPV亚型中两者均高：HPV6／11为66．67％（8／12例），HPV16／18为41．67％（5／12例）。结论：巨大型尖锐湿疣是一类无论在组织形态、生物学特征和病原学基础等方面均有异于普通尖锐湿疣的特殊类型。     

尖锐湿疣组织中人乳头状瘤病毒感染与生存素和增殖细胞核抗原的表达

目的 探讨人乳头状瘤病毒（HPV）6／11、16／18在尖锐湿疣（CA）组织中的感染情况及其与生存素和增殖细胞核抗原（PCNA）表达的关系。方法 HPV分型PCR检测试剂盒检测HPV6／11、16／18在41例尖锐湿疣组织、23例正常皮肤组织中的表达情况，同时用SP免疫组化法检测生存素及PCNA蛋白的表达。结果 ①正常对照组未检测到HPV6／11、16／18感染；HPV6／11在尖锐湿疣中的感染率为87．80％（36／41），与正常对照组比较差异有统计学意义（P〈0．005）；HPV16／18在尖锐湿疣中的感染率为19．51％（8／41），与正常对照组比较差异无统计学意义（P〉0．05）。②生存素和PCNA在尖锐湿疣组织中的阳性率分别为53．66％（22／41）和87．80％（36／41），在正常皮肤组织中的阳性率分别为8．70％（2／23）和47．83％（11／23）。尖锐湿疣组中生存素和PCNA表达的阳性率与正常对照组比较差异均有统计学意义．且尖锐湿疣中两者的阳性表达呈正相关（P=0．009）。③生存素及PCNA在有HPV6／11感染患者中的表达明显强于无HPV6/11感染患者。结论 HPV感染可上调生存素与PCNA的表达。     

外阴白斑和外阴鳞癌中基底膜蛋白的研究

目的：研究层黏连蛋白(LN)和IV型胶原在外阴白斑和外阴鳞癌中的表达。方法：采用SABC免疫组化法，对59例外阴白斑和9例外阴鳞癌标本进行基底膜蛋白染色。结果：正常皮肤组织、外阴白斑(增生型、硬化萎缩型和混合型)LN和IV型胶原基底膜染色密度高，呈连续线状。LN和IV型胶原的染色密度和基底膜的连续性与外阴白斑的异常增生度及鳞癌的分化程度(由高分化到低分化)呈负相关。结论：基底膜蛋白的表达和分布与外阴白斑分型有关，外阴鳞癌和不典型增生组织中表达阳性率明显低于外阴白斑各型，基底膜蛋白有可能作为早期诊断癌前病变的一种生物学指标。     

hTERT基因转染激活人毛乳头细胞端粒酶的实验研究

目的:明确外源性人端粒酶反转录酶(hTERT)基因转染能否激活体外培养人毛乳头细胞(DPC)的端粒酶.方法:采用脂质体转染法,将空载体质粒pIRES2-EGFP和含有hTERT基因的质粒pIRES2-EGFP-hTERT分别导入体外培养的正常人DPC,经G418筛选得到阳性克隆,连续传代培养.应用反转录(RT)-PCR法检测hTERT mRNA的表达,端粒重复序列扩增(TRAP)-ELISA法检测细胞端粒酶活性.结果:未转染DPC和空载体转染细胞(DPC-EGFP)无hTERT mRNA表达,端粒酶活性为阴性;而外源性hTERT基因转染细胞(DPC-hTERT)稳定表达hTERT mRNA,同时端粒酶活性转为阳性.结论:外源性hTERT基因转染能够激活体外培养人DPC的端粒酶,为建立永生化细胞系奠定基础.     

Serological association of beta and gamma human papillomaviruses with squamous cell carcinoma of the skin

Background  Cutaneous human papillomaviruses (HPVs) may play a role in the development of squamous cell carcinomas (SCC) of the skin.
Objectives  Available serological studies on HPV and skin SCC have analysed only few HPV types from the phylogenetic genus beta. The potential association of cutaneous HPV types from the genera alpha, gamma, mu and nu with skin SCC has not been thoroughly analysed so far.
Methods  Using multiplex serology, a method that allows analysing sera for antibodies to up to 100 different antigens simultaneously, we re-analysed an SCC case–control study in immunocompetent individuals (43 cases, 77 controls) for antibodies to L1 capsid proteins of 29 cutaneous and two mucosal HPV types from five different genera.
Results  Significantly increased SCC risks were observed for the beta HPV types 15, 17 and 38, as well as for the gamma HPV type 50, with type-specific odds ratios (ORs) ranging from 2·6 to 3·4. Significant associations were also found in cases of seropositivity for any type of the beta 2 species (OR 3·3, 95% confidence interval [CI] 1·2–8·7) and for any type of the gamma genus (OR 3·1, 95% CI 1·1–8·6). With regression models that included all HPV types and forward stepwise selection, two gamma HPV types (HPV 95, OR 25, 95% CI 1·2–509; HPV 50, OR 3·6, 95% CI 1·4–9·4) were each significantly associated with skin SCC.
Conclusions  Our study confirms a possible role of cutaneous HPV in the development of skin SCC. Future studies should include skin HPV types from more than only the beta genus, especially gamma types.     

Lichen sclerosus is frequently present in penile squamous cell carcinomas but is not always associated with oncogenic human papillomavirus

BACKGROUND: Penile squamous cell carcinoma (SCC) may occur on pre-existing lesions of lichen sclerosus (LS). However, the prevalence of histological changes of LS in penile SCC is not well established. Moreover, mucosal oncogenic human papillomaviruses (HPVs) are sometimes detected in penile SCC, but have not been systematically sought in LS-associated penile SCC. OBJECTIVES: To establish the prevalence of LS histological changes and of mucosal oncogenic HPV in a series of patients with penile SCC. METHODS: Consecutive cases of histologically proven penile SCC from a single university hospital over a 14-year period were retrospectively selected and reviewed. Histological signs of LS were systematically sought. HPV was detected by polymerase chain reaction (PCR) amplification of DNA from paraffin-embedded skin samples using general primers GP5+/GP6+ (allowing detection of mucosal HPV) and oncogenic type 16-, 18-, 31- and 33-specific primers. RESULTS: Eighteen cases of penile SCC were found. The mean +/- SD age of patients at diagnosis was 67.3 (14.5 years). In eight of 18 (44%) cases, SCC was associated with histological features of LS. Seventeen skin biopsy specimens of SCC (nine without and eight with LS histology) were subjected to PCR amplification for HPV. Mucosal HPV was detected in six of them (35%). Five of nine SCCs without histological features of LS were positive for mucosal HPV: three with HPV type 16 and two with only general primers. In contrast, all eight SCCs associated with LS were negative for oncogenic HPV types, although one was positive with general primers. CONCLUSIONS: Penile SCC seems to be frequently associated with LS histological changes. As with vulval SCC, we found that non-LS-associated penile SCC tended to be frequently associated with oncogenic HPV infection, whereas LS-associated penile SCC was not. Larger series are needed to confirm this association.     

Vulvar squamous cell carcinoma and lichen sclerosus

There are two clinicopathological types of vulvar squamous cell carcinoma, human papillomavirus (HPV)-positive and HPV-negative, which can be distinguished to some degree on routine histology. Human papillomavirus-positive carcinomas account for one-quarter to one-third of cases, occur in women on average 20 years younger than in HPV-negative, and are associated with multiple lower genital tract neoplasia. Human papillomavirus negative carcinoma is linked to lichen sclerosus. Of all carcinomas, 7-96% show lichen sclerosus in skin adjacent to the carcinoma, the majority being the first presentation of lichen sclerosus, and up to 5% of patients with lichen sclerosus develop carcinoma after long-term follow up. Where lichen sclerosus is associated with malignancy, it is often hyperplastic, may show a subtle form of intraepithelial neoplasia termed 'differentiated vulvar intraepithelial neoplasia', and may lose its pathognomonic oedematous-hyaline layer. The local additional factors causing lichen sclerosus to develop malignancy on the vulva are not known.