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目的针对外阴上皮内非瘤变(nonneoplastic epithelial disorders of vulva,NNEDV)难治疗易复发的特点,应用免疫组化方法检测外阴白色病变组织中人表皮生长因子受体-2(human epidermal growth factor receptor 2,HER-2)/neu和p16蛋白表达水平的变化,并探讨其与外阴白色病变发生、发展的关系,以了解外阴白色病变的发病和治疗机制。方法选择煤炭总医院妇产科2014年5月至2016年1月NNEDV组织36份为研究组,其中硬化性苔癣(lichen sclerosus,LS)10例,鳞状上皮细胞增生(squamous hyperplasia,SH)18例,SH合并LS 8例;另选择阴道前后壁修补术者标本12份为正常对照组。应用免疫组化方法检测HER-2/neu和p16蛋白质的表达,并分析其与NNEDV发病的关系。结果发现p16表达率在正常外阴皮肤为25%,高于外阴白色病变患者的11.1%,差异无统计学意义(P>0.05)。LS和SH组织中p16蛋白阳性表达率分别为10%和5.6%,差异无统计学意义(P>0.05)。正常外阴皮肤组织HER-2/neu蛋白表达率为8.3%,外阴白色病变患者为55.5%,明显高于正常外阴者(P<0.05)。LS和SH组织中,HER-2/neu蛋白阳性表达率分别为40%和66.7%,两者比较差异有统计学意义(P<0.05)。结论原癌基因HER-2/neu和抑癌基因p16是调控细胞增殖周期进程的重要因子,其突变或缺失可能导致蛋白异常表达。它们参与了外阴异常增殖过程,在NNEDV甚至外阴上皮内瘤变及外阴鳞癌的发生、发展过程中起重要作用。
Objective To investigate the characteristics of refractory relapse of nonneoplastic epithelial disorders of vulva (NNEDV), immunohistochemistry was used to detect the expression of human epidermal growth factor receptor 2 , HER-2) / neu and p16 protein expression, and explore the relationship with the occurrence and development of white lesions of vulva to understand the pathogenesis of vulvar white lesions and treatment mechanism. Methods Forty-five NNEDV tissues from May 2014 to January 2016 in the General Hospital of Coal Mine were selected as the study group, including 10 cases of lichen sclerosus (LS), 10 cases of squamous hyperplasia (SH) 18 cases, SH combined with 8 cases of LS; other vaginal anterior and posterior wall repair of 12 specimens were normal control group. Immunohistochemistry was used to detect the expression of HER-2 / neu and p16 protein, and to analyze its relationship with the occurrence of NNEDV. The results showed that the expression rate of p16 was 25% in normal vulvar skin, which was higher than 11.1% of patients with white lesions of vulva, the difference was not statistically significant (P> 0.05). The positive rates of p16 protein in LS and SH tissues were 10% and 5.6%, respectively, with no significant difference (P> 0.05). Normal vulvar skin tissue HER-2 / neu protein expression rate of 8.3%, 55.5% of patients with vulvar white lesions, significantly higher than the normal vulva (P <0.05). The positive rates of HER-2 / neu protein expression in LS and SH tissues were 40% and 66.7% respectively, with significant difference between the two groups (P <0.05). Conclusions Proto-oncogene HER-2 / neu and tumor suppressor gene p16 are important factors in regulating cell cycle progression. Mutations or deletions may lead to abnormal protein expression. They participate in the process of abnormal proliferation of the vulva and play an important role in the occurrence and development of NNEDV and even vulvar intraepithelial neoplasia and vulvar squamous cell carcinoma.