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HPV与FHIT在鼻内翻性乳头状瘤中的相关性研究

发布时间:2019-03-31 10:55
【摘要】:目的 鼻腔鼻窦内翻性乳头状瘤(sinonasal inverted papilloma, SNIP)是来源于鼻腔鼻窦上皮细胞的良性肿瘤,以潜在的复发和癌变倾向为其特征。近年来,随着外科手术技术的提高,尤其是鼻内镜手术技术的提高,使SNIP的治愈率得到了很大的提高。但其复发及恶变的病因和病理目前仍未完全阐明。人乳头瘤病毒(human papilloma virus, HPV)是与人类肿瘤的关系最为明确的病毒之一。它主要侵犯人皮肤粘膜的上皮组织,引起皮肤粘膜上皮的良恶性增生。脆性组氨酸三联体基因(fragile histidine triad, FHIT)作为与环境致癌物密切相关的抑癌基因,在人类许多肿瘤组织和细胞系中表现为高频率缺失和异常转录。本研究通过对SNIP病例进行临床分析,利用多聚酶链反应和免疫组化技术,对鼻腔鼻窦内翻性乳头状瘤中HPV感染与FHIT基因的表达进行相关性研究。探讨SNIP复发及恶变的发病机制,为临床进一步预测肿瘤的生物学行为,进一步优化治疗方案提供依据。 方法 1、收集2006年6月—2011年6月在天津市环湖医院经病理确诊的临床及病理资料完整的患者70例。按病理类型分为鼻腔鼻窦内翻性乳头状瘤(SNIP)组50例,鼻腔鼻窦鳞状细胞癌(鳞癌)组20例,另收集正常下鼻甲黏膜组织(正常)组20例作为对照。所有患者经病理诊断复查核实。 2、以病例及肿瘤组织为对象进行研究,进行临床资料,多聚酶链反应,以及免疫组化检测分析: (1) SNIP组又按是否复发分为原发组30例,复发组20例;按Krouse临床分期:Ⅰ期11例,1Ⅱ期22例,Ⅲ期14例,Ⅳ期3例。 (2)应用多聚酶链反应(polymerase chain reaction, PCR)技术,检测其HPV16,18两个型别的HPV-DNA。 (3)应用免疫组化技术了解FHIT基因蛋白表达的情况 (4)分析年龄、临床分期、是否复发以及恶性病例中HPV感染与FHIT基因表达情况以及之间的相关性。 3、采用SPSS17.0软件对数据进行统计学处理。 结果 (1)HPV在SNIP组阳性感染率与正常组差别有统计学意义(P0.01),与鳞癌组差别无统计学意义(P0.05),并随鼻腔鼻窦内翻性乳头状瘤的临床分期递增,而且与患者年龄有关,与肿瘤是否复发有关。 (2)SINP组FHIT基因与正常组中的阳性表达率差异有统计学意义(P0.01),与鼻腔鼻窦鳞癌的差异无统计学意义(P0.05),与鼻腔鼻窦内翻性乳头状瘤中临床分期,患者年龄无关。与肿瘤是否复发无关。 (3)FHIT基因的失活和HPV感染在鼻腔鼻窦内翻性乳头状瘤组织中的表达呈正相关(P0.051。 结论 1、HPV感染与SNIP的发病有密切关系,提示HPV感染在NIP发病机制上有一定作用。高危型HPV感染可能预示SNIP复发及恶变的风险增加。这就要求术者采取相应的手术术式,彻底切除病变组织。并密切随访,以减少鼻内翻性乳头状瘤的复发及恶变。 2、FHIT的低表达或不表达可能是鼻腔鼻窦内翻性乳头状瘤复发和恶变早期阶段的重要事件。作为一个抑癌基因,其表达下降或不表达对鼻腔鼻窦内翻性乳头状瘤的发生、发展起了重要作用,可能是鼻腔鼻窦内翻性乳头状瘤恶性转化过程中的关键一步。 3、HPV感染可能通过基因整合使FHIT基因表达缺失或失活,HPV的感染与FHIT基因的表达异常在鼻腔鼻窦内翻性乳头状瘤的发生发展中起协同作用,可能为鼻腔鼻窦内翻性乳头状瘤的诊疗提供新的靶点。
[Abstract]:Purpose The sinonasal inverted papiloma (SNIP) of the nasal cavity of the nasal cavity is a benign tumor derived from the nasal epithelial cells of the nasal cavity. In recent years, with the improvement of the surgical technique, especially the improvement of the surgical technique of the nasal endoscope, the cure rate of the SNIP is greatly improved. High. But the cause and pathology of the recurrence and the malignant change are still not complete. Human papiloma virus (HPV) is the most specific virus in relation to human tumors. I. It mainly encroaches on the epithelial tissue of the human skin mucosa, causing the benign and malignant growth of the skin mucosa epithelium. The fragile histidine triad triad (FHIT) is a tumor suppressor which is closely related to the environmental carcinogen, and is shown as high-frequency deletion and abnormal rotation in many human tumor tissues and cell lines. The purpose of this study was to study the relationship between the expression of the HPV infection and the FHIT gene in the nasal cavity of the nasal cavity by means of the clinical analysis of the SNIP cases, the polymerase chain reaction and the immunohistochemical technique. To investigate the mechanism of SNIP recurrence and malignant change, to further predict the biological behavior of the tumor and to further optimize the treatment plan. It was reported. Method 1. The clinical and pathological data were collected from June,2006 to June,2011 in the Tianjin Huanhu Hospital. 70 of the patients were divided into the nasal cavity of the nasal cavity,50 cases of the SNIP group,20 cases of the squamous cell carcinoma of the nasal cavity of the nasal cavity and 20 cases of the normal nasal mucosa tissue (normal). The case was used as a control. All patients were diagnosed by pathology Check and verify.2. Carry out the study on the case and the tumor tissue as the target, and carry out clinical data, polymerase chain reaction, and maintenance-free. The results showed that: (1) The SNIP group was divided into 30 cases of primary group and 20 cases of recurrent group. 1 case,22 cases in phase 鈪,

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