【摘要】：目的 鼻腔鼻竇內(nèi)翻性乳頭狀瘤(sinonasal inverted papilloma, SNIP)是來源于鼻腔鼻竇上皮細(xì)胞的良性腫瘤,以潛在的復(fù)發(fā)和癌變傾向為其特征。近年來,隨著外科手術(shù)技術(shù)的提高,尤其是鼻內(nèi)鏡手術(shù)技術(shù)的提高,使SNIP的治愈率得到了很大的提高。但其復(fù)發(fā)及惡變的病因和病理目前仍未完全闡明。人乳頭瘤病毒(human papilloma virus, HPV)是與人類腫瘤的關(guān)系最為明確的病毒之一。它主要侵犯人皮膚粘膜的上皮組織,引起皮膚粘膜上皮的良惡性增生。脆性組氨酸三聯(lián)體基因(fragile histidine triad, FHIT)作為與環(huán)境致癌物密切相關(guān)的抑癌基因,在人類許多腫瘤組織和細(xì)胞系中表現(xiàn)為高頻率缺失和異常轉(zhuǎn)錄。本研究通過對SNIP病例進(jìn)行臨床分析,利用多聚酶鏈反應(yīng)和免疫組化技術(shù),對鼻腔鼻竇內(nèi)翻性乳頭狀瘤中HPV感染與FHIT基因的表達(dá)進(jìn)行相關(guān)性研究。探討SNIP復(fù)發(fā)及惡變的發(fā)病機(jī)制,為臨床進(jìn)一步預(yù)測腫瘤的生物學(xué)行為,進(jìn)一步優(yōu)化治療方案提供依據(jù)。 方法 1、收集2006年6月—2011年6月在天津市環(huán)湖醫(yī)院經(jīng)病理確診的臨床及病理資料完整的患者70例。按病理類型分為鼻腔鼻竇內(nèi)翻性乳頭狀瘤(SNIP)組50例,鼻腔鼻竇鱗狀細(xì)胞癌(鱗癌)組20例,另收集正常下鼻甲黏膜組織(正常)組20例作為對照。所有患者經(jīng)病理診斷復(fù)查核實。 2、以病例及腫瘤組織為對象進(jìn)行研究,進(jìn)行臨床資料,多聚酶鏈反應(yīng),以及免疫組化檢測分析： (1) SNIP組又按是否復(fù)發(fā)分為原發(fā)組30例,復(fù)發(fā)組20例；按Krouse臨床分期：Ⅰ期11例,1Ⅱ期22例,Ⅲ期14例,Ⅳ期3例。 (2)應(yīng)用多聚酶鏈反應(yīng)(polymerase chain reaction, PCR)技術(shù),檢測其HPV16,18兩個型別的HPV-DNA。 (3)應(yīng)用免疫組化技術(shù)了解FHIT基因蛋白表達(dá)的情況 (4)分析年齡、臨床分期、是否復(fù)發(fā)以及惡性病例中HPV感染與FHIT基因表達(dá)情況以及之間的相關(guān)性。 3、采用SPSS17.0軟件對數(shù)據(jù)進(jìn)行統(tǒng)計學(xué)處理。 結(jié)果 (1)HPV在SNIP組陽性感染率與正常組差別有統(tǒng)計學(xué)意義(P0.01),與鱗癌組差別無統(tǒng)計學(xué)意義(P0.05),并隨鼻腔鼻竇內(nèi)翻性乳頭狀瘤的臨床分期遞增,而且與患者年齡有關(guān),與腫瘤是否復(fù)發(fā)有關(guān)。 (2)SINP組FHIT基因與正常組中的陽性表達(dá)率差異有統(tǒng)計學(xué)意義(P0.01),與鼻腔鼻竇鱗癌的差異無統(tǒng)計學(xué)意義(P0.05),與鼻腔鼻竇內(nèi)翻性乳頭狀瘤中臨床分期,患者年齡無關(guān)。與腫瘤是否復(fù)發(fā)無關(guān)。 (3)FHIT基因的失活和HPV感染在鼻腔鼻竇內(nèi)翻性乳頭狀瘤組織中的表達(dá)呈正相關(guān)(P0.051。 結(jié)論 1、HPV感染與SNIP的發(fā)病有密切關(guān)系,提示HPV感染在NIP發(fā)病機(jī)制上有一定作用。高危型HPV感染可能預(yù)示SNIP復(fù)發(fā)及惡變的風(fēng)險增加。這就要求術(shù)者采取相應(yīng)的手術(shù)術(shù)式,徹底切除病變組織。并密切隨訪,以減少鼻內(nèi)翻性乳頭狀瘤的復(fù)發(fā)及惡變。 2、FHIT的低表達(dá)或不表達(dá)可能是鼻腔鼻竇內(nèi)翻性乳頭狀瘤復(fù)發(fā)和惡變早期階段的重要事件。作為一個抑癌基因,其表達(dá)下降或不表達(dá)對鼻腔鼻竇內(nèi)翻性乳頭狀瘤的發(fā)生、發(fā)展起了重要作用,可能是鼻腔鼻竇內(nèi)翻性乳頭狀瘤惡性轉(zhuǎn)化過程中的關(guān)鍵一步。 3、HPV感染可能通過基因整合使FHIT基因表達(dá)缺失或失活,HPV的感染與FHIT基因的表達(dá)異常在鼻腔鼻竇內(nèi)翻性乳頭狀瘤的發(fā)生發(fā)展中起協(xié)同作用,可能為鼻腔鼻竇內(nèi)翻性乳頭狀瘤的診療提供新的靶點。
[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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