【摘要】：研究背景： P16是腫瘤抑制基因,其編碼產(chǎn)生的P16蛋白直接參與細(xì)胞周期的調(diào)節(jié)，p16蛋白與多種腫瘤相關(guān)。P16通過缺失、高甲基化和點(diǎn)突變導(dǎo)致基因失活在腫瘤的發(fā)生發(fā)展中發(fā)揮重要作用。 目的： 1.探討P16蛋白在宮頸上皮內(nèi)瘤變的表達(dá)及相關(guān)性。 2.研究P16基因外顯子的缺失與宮頸上皮內(nèi)瘤變的關(guān)系。 方法： 1.免疫組化染色檢測P16蛋白的表達(dá)情況：選取福建醫(yī)科大學(xué)附屬第一醫(yī)院2011年6月-2013年2月宮頸手術(shù)切除及活檢標(biāo)本407例，包括正常宮頸鱗狀上皮81例、CIN I95例、CIN II74例、CINIII77例、宮頸癌80例。 2. PCR擴(kuò)增法檢測P16基因外顯1、2和3缺失情況：選取福建醫(yī)科大學(xué)附屬第一醫(yī)院2011年6月-2013年2月宮頸手術(shù)切除標(biāo)本80例，包括正常宮頸鱗狀上皮10例、CIN I10例、CIN II20例、CINIII20例、宮頸癌20例。 結(jié)果： 1．隨著宮頸鱗狀上皮瘤變的進(jìn)展，P16蛋白表達(dá)率逐漸升高：CIN Ⅰ組中陽性表達(dá)率為31.58%，，CIN Ⅱ組中陽性表達(dá)率為62.16%，CIN Ⅲ組中陽性表達(dá)率為93.50%，癌組中陽性表達(dá)率為100.00% 2.隨著宮頸鱗狀上皮瘤變的進(jìn)展，P16蛋白表達(dá)范圍逐漸擴(kuò)大：：CIN Ⅰ級陽性細(xì)胞主要局限于鱗狀上皮下1/3層；CIN Ⅱ級擴(kuò)展至鱗狀上皮的下2/3；CIN Ⅲ級陽性細(xì)胞表達(dá)于上皮全層。 3.隨著宮頸鱗狀上皮瘤變的進(jìn)展，P16蛋白強(qiáng)陽性表達(dá)率逐漸增加：CINⅠ級為1.05%，CINⅡ級為5.41%，CINⅢ為50.65%，癌中p16強(qiáng)陽性表達(dá)率為85.00%。 4.在宮頸鱗狀上皮瘤變過程中，P16基因發(fā)生外顯子缺失：共檢測39例外顯子缺失的病例，其中11例外顯子1缺失、26例外顯子2缺失及2例外顯子3缺失。9例同時存在外顯子1和2缺失。 5. P16基因外顯子2的缺失率顯著高于外顯子1和外顯子3的缺失率。結(jié)論 1. P16蛋白表達(dá)參與宮頸鱗狀上皮瘤變的進(jìn)展過程，免疫組化染色結(jié)果可以協(xié)助判斷宮頸病變情況。 2. P16基因外顯子的缺失可能參與與宮頸鱗狀上皮的瘤變。
[Abstract]:Background: P16 is a tumor suppressor gene. The P16 protein encoded by P16 protein is directly involved in the regulation of cell cycle. P16 protein is associated with a variety of tumors through deletion. Gene inactivation due to hypermethylation and point mutation plays an important role in tumorigenesis and development. Objective: 1. To investigate the expression and correlation of P16 protein in cervical intraepithelial neoplasia. 2. To study the relationship between deletion of P16 gene exon and cervical intraepithelial neoplasia. Methods: 1. Immunohistochemical staining was used to detect the expression of P16 protein. From June 2011 to February 2013, 407 specimens of cervical excision and biopsy were collected from the first affiliated Hospital of Fujian Medical University, including 81 cases of normal cervical squamous epithelium, 95 cases of cin I and 77 cases of cin II I. 80 cases of cervical cancer PCR amplification method was used to detect the deletion of P16 gene. 80 cases of cervical excision were selected from the first affiliated Hospital of Fujian Medical University from June 2011 to February 2013, including 10 cases of cervical squamous epithelium with cin I 10 cases of cin II20 and 20 cases of CINIII I. There were 20 cases of cervical cancer. Results: 1. With the progression of cervical squamous epithelioma, the expression rate of P16 protein increased gradually. The positive expression rate of P16 protein was 31.58% in cin 鈪

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