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人乳头瘤病毒早期蛋白E6(HPV16/18 - E6)和细胞周期标志物P16(INK4a)是沙特阿拉伯卡西姆地区子宫颈癌有用的预后标志物。

Human papilloma virus early proteins E6 (HPV16/18-E6) and the cell cycle marker P16 (INK4a) are useful prognostic markers in uterine cervical carcinomas in Qassim Region--Saudi Arabia.

作者信息

Omran O M, AlSheeha M

机构信息

Department of Pathology, College of Medicine, Assiut University, Assiut, Egypt,

出版信息

Pathol Oncol Res. 2015 Jan;21(1):157-66. doi: 10.1007/s12253-014-9801-y. Epub 2014 Jun 13.

Abstract

Cervical cancer is a common and an important public health problem for adult women in developing countries. In contrast, cervical cancer incidence is low in Saudi Arabia. High-risk types of human papilloma viruses (HPV16 and HPV18) are the most significant risk factors for cervical cancer. HPV16/18-E6 oncoprotein is associated with HPV etiology, viral persistence and epithelial transformation. Cell cycle protein p16 INK4a (p16) plays an important role in the pathophysiology of cervical carcinomas. The aims of this study were to investigate the expression of HPV16/18-E6 and p16 in uterine cervical carcinomas in Qassim Region--Saudi Arabia, and to relate the results to the established clinicopathological prognostic parameters (age of the patient, educational level, birth control methods, number of pregnancy, smoking status, degree of histological differentiation, clinical stage, and lymph node metastasis) The study included 40 specimens of uterine cervical squamous cell carcinomas diagnosed and confirmed by biopsy. Histopathological classification of cervical tumors cases was performed according to the International Federation of Gynecology and Obstetrics (FIGO). Immunohistochemical analysis for HPV16/18-E6 and p16 were carried out on formalin-fixed paraffin-embedded sections of cervical tissues using avidin-biotin peroxidase method. There was a significant statistical correlation between HPV16/18-E6 expression in cervical carcinoma and nationality, smoking status and size of the tumor. HPV16/18-E6 oncoprotein expression in normal lymphocytes and endothelial cells in the tumor tissues and the adjacent normal cervical tissues suggest the possibility that HPV infection might spread to other organs through blood circulation. P16 expression has been correlated with high grade, stage of cervical SCC and HPV16/18-E6 expression. The current study supports the critical function of p16 and HPV16/18-E6 as specific markers for cervical carcinoma. However the potential for usage of p16 and HPV16/18-E6 as prognostic markers will require detailed follow data for a larger group of patients.

摘要

宫颈癌是发展中国家成年女性常见且重要的公共卫生问题。相比之下,沙特阿拉伯的宫颈癌发病率较低。高危型人乳头瘤病毒(HPV16和HPV18)是宫颈癌最重要的危险因素。HPV16/18-E6癌蛋白与HPV病因、病毒持续存在及上皮转化相关。细胞周期蛋白p16INK4a(p16)在宫颈癌的病理生理学中起重要作用。本研究的目的是调查沙特阿拉伯卡西姆地区子宫颈癌中HPV16/18-E6和p16的表达情况,并将结果与既定的临床病理预后参数(患者年龄、教育水平、避孕方法、妊娠次数、吸烟状况、组织学分化程度、临床分期和淋巴结转移)相关联。该研究纳入了40例经活检诊断并确诊的子宫颈鳞状细胞癌标本。宫颈肿瘤病例的组织病理学分类根据国际妇产科联盟(FIGO)进行。使用抗生物素蛋白-生物素过氧化物酶法对宫颈组织的福尔马林固定石蜡包埋切片进行HPV16/18-E6和p16的免疫组织化学分析。宫颈癌中HPV16/18-E6表达与国籍、吸烟状况和肿瘤大小之间存在显著的统计学相关性。肿瘤组织及相邻正常宫颈组织中正常淋巴细胞和内皮细胞中的HPV16/18-E6癌蛋白表达提示HPV感染可能通过血液循环扩散到其他器官的可能性。P16表达与宫颈鳞状细胞癌的高级别、分期及HPV16/18-E6表达相关。当前研究支持p16和HPV16/18-E6作为宫颈癌特异性标志物的关键作用。然而,将p16和HPV16/18-E6用作预后标志物的潜力需要更多患者的详细随访数据。

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