【作者】 朱少君；

【导师】 苏勤；

【作者基本信息】 中国人民解放军第四军医大学 ， 病理学与病理生理学， 2003， 硕士

【摘要】 外阴尖锐湿疣是由人乳头状瘤病毒(human papillomavims，HPV)感染引起的鳞状上皮增生性病变，主要经性活动传播，多数病变的致病因子是低危型HPV(主要是HPV6/11)。其发病高峰年龄为20～30岁，70％在30岁以下，但老年及儿童也可发病。尖锐湿疣的性质至今未确定，有的作者把它放在外阴炎症中讨论，有的则把这种病变归入鳞状上皮良性肿瘤的范畴，但缺乏确切证据。 为了探讨女性外阴尖锐湿疣的性质，我们结合使用显微解剖和雄激素受体(androgen receptor，AR)基因位点的克隆性检测，检查了以下组织的克隆组成：1)尖锐湿疣组织增生鳞状上皮；2)结构基本正常宫颈鳞状上皮；3)宫颈癌癌组织；4)子宫平滑肌瘤组织。上述4种组织分析时均取其临近的结构基本正常组织作对照(正常宫颈上皮取其旁间质作对照)。此外，对于多克隆和单克隆性起源的尖锐湿疣标本，分别计算其所有视野的核分裂数和凋亡小体数，以观察两种不同起源的病变在细胞动力学上的差别。 对福尔马林固定、石蜡包埋的子宫平滑肌瘤组织进行的检测显示，适于分析的4例标本均为单克隆性起源，这与用新鲜标本得到的结果一致，说明我们用石蜡包埋组织进行克隆性分析是可行的。结合使用显微解剖和克隆性检测表明，7例宫颈癌癌组织均为单克隆性起源，而5例具多态性的结构正常的宫颈鳞状上皮组织均为多克隆性增生，提示肿瘤性病变与反应性增生的细胞组成不同，前者为单克隆性而后者为多克隆性细胞群体。由于显微解剖的应用最大程 第四军医大学硕士学位论文度减少了病变的污染，从而增加了这一分析的准确性。 在收集的 95例尖锐湿疣标本中，76例扩增成功，其中 62例（81．5O）可检测到 AR位点的多态性；在适于分析的 54例中，11例显示出（20％）AR位点限制性片段长度多态性丢失，其余43例（80％）无多态性丢失，提示前者已经是单克隆性而后者依然是多克隆性细胞增生。我们的数据还表明，上述单克隆性病变的核分裂指数明显高于多克隆性病变，但二者的凋亡小体计数差别不显著。 因此我们认为，大部分尖锐湿疣属于多克隆性病变，是反应性增生；少部分是克隆性增生，可能已经属于真性肿瘤。更多还原

【Abstract】 Condyloma acuminata is a type of proliferative lesions of squamous epithelium, believed to be caused by chronic infection of human papillomavirus (HPV), frequently of types 6 and 11, and considered a sex-transmitted disease. The lesion is found most frequently in patients aging 20 to 30 years. Some rare cases were found in old patients and children. The nature of condyloma acuminata remains unknown. Many authors consider it a inflammatory reaction. Some authors, however, put the lesion in the category of squamous epithelial neoplasia.To demonstrate the clonality status of condyloma acuminata of vulva, we use an assay based on microdissection and inactivation mosaicism of the length polymorphic X chromosomes at the androgen receptor (AR) locus to examine the clonality of the following tissues: 1) epithelial components of the condyloma lesions with the stroma components as parallel controls; 2) normal epithelial components from the cervix with the stroma components as parallel controls; 3) cervix carcinomas with the stroma components as controls; 4) uterine leiomyomas with the peritumorous normal smooth muscle tissues as controls. Furthermore, we calculate the mitotic indices and apoptotic bodies counts in all monoclonal and polyclonal condyloma lesions for possible changes in cellular kinetics.To ensure the reliability of the assay, we examined the clonality of theformalin-fixed, paraffin-embedded tissues of uterine leiomyomas. Four samplessuitable for the clonality test showed monoclonality being in agreement with our previous results obtained using fresh tissues. This demonstrates that formalin-fixed, paraffin-embedded tissue samples can be used for the assay. Seven samples of cervical carcinoma, suitable for the test, were microdissected and demonstrated to be of monoclonal origin, while five samples of normal epithelial components of cervix, obtained also by microdissection, were shown to be polyclonal. These data illustrated the difference in clonal composition between the neoplastic and the normal epithelial tissues. Meanwhile, application of microdissection can reduce interference from the admixed non-neoplastic cell, and enhance accuracy of the assay.A total number of 95 condyloma samples were examined. Seventy-six samples were amplified successfully and 62 (81.5%) of them were shown to carry length polymorphism at the AR locus. Fifty-four samples were suitable for the clonality test. Among them, 43 (80%) were shown to be polyclonal. Loss of X-chromosome inactivation mosaicism was found in 11 (20%) lesions, reflecting their monoclonality. Mitotic indices were higher in the monoclonal condyloma lesions than those in the polyclonal lesions, but no significant difference was found between their apoptotic body counts.In summary, most of vulvar condyloma acuminata are polyclonal, thereby being responsive proliferative lesions. About 20% of the condyloma lesions, however, show monoclonal cell expansion, and these may be already neoplastic.更多还原