宫颈癌组织中FR-α与Ki-67的表达及其相关性研究

发布时间：2018-05-04 05:21

  本文选题：FR-α蛋白 + Ki-67　； 参考：《河北医科大学》2014年硕士论文

【摘要】：目的：宫颈癌(Cervical Cancer)是最常见的妇科恶性肿瘤之一，发病率居女性恶性肿瘤的第二位,仅次于乳腺癌,其病理类型常见的有鳞癌、腺癌、腺鳞癌，其发病原因主要与以下因素有关：1.高危型HPV感染；2.性行为及分娩次数；3.沙眼衣原体、单纯疱疹病毒II型、滴虫等病原体的感染起着协同作用；4.吸烟以及营养不良、卫生条件差等。发病早期的宫颈癌常无明显的症状和体征，宫颈光滑或难与宫颈柱状上皮异位相鉴别。颈管型患者因宫颈外观正常易漏诊或误诊。其转移途径主要为直接蔓延及淋巴转移，血行转移较少见。在细胞代谢、DNA合成和修复以及癌细胞快速增殖分裂过程中叶酸发挥着重要作用，快速分裂癌细胞的DNA合成对于叶酸有很高的需求，所以近年来转运叶酸进入细胞内的叶酸受体α成为人们的研究热点。叶酸受体是一种膜结合蛋白，它在结合运输生理水平的叶酸到细胞内的过程中发挥着重要的作用，其在正常组织中低表达，在肿瘤细胞膜表面高度表达，叶酸受体（FR）分为FR-α、FR-β、FR-γ，其中FR-α高表达于黏液腺癌中，包括卵巢腺癌、子宫腺癌、宫颈腺癌、睾丸绒毛膜癌和某些脑肿瘤中，并且少量地表达于肾、结肠及心脏等癌症中。Ki-67是存在于增殖细胞核的与细胞增殖密切相关的核蛋白，作为评价细胞增殖的标记物，现已广泛地应用于肿瘤的研究和探讨中。本实验用免疫组织化学法（immunohistochemistry）检测宫颈癌组织中FR-α蛋白及Ki-67的表达，探讨二者的关系及其临床意义。 方法：采用免疫组织化学PV法检测正常宫颈组织、宫颈上皮内瘤变组织以及宫颈癌组织中FR-α蛋白表达及Ki-67的表达。分实验组：宫颈癌33例（其中宫颈癌I期11例，宫颈癌II期12例，，宫颈癌III期10例）。对照组：正常宫颈组织30例，宫颈上皮内瘤变组织42例，阳性表达判断：细胞胞浆内出现棕黄色颗粒为准，参考Soslow RA和刘祖国等[1][2]提到的方法，采用免疫组化评分法来判定结果，先按染色强度评分：未见染色为0分，淡黄色为1分,棕黄色为2分，棕褐色为3分；再按阳性细胞所占百分比评分：随机选取高倍镜（×200）下观察5个视野，每个视野计数100个细胞，进行阳性细胞数分级，0-1%=0，1-10%=1，10-50%=2，50-80%=3，80-100%=4)。两项评分乘积所得总分（IHS）进行结果判定：IHS0分为（-），IHS1~4分为（+），IHS5~8分为（++），IHS9~12分为（+++）。Ki-67结果判断：细胞胞浆内出现棕黄色颗粒为准，参考Soslow RA和刘祖国等[1][2]提到的方法，采用免疫组化评分法来判定结果，先按染色强度评分：未见染色为0分，淡黄色为1分，棕黄色为2分，棕褐色为3分；再按阳性细胞所占百分比评分：随机选取高倍镜（×200）下观察5个视野，每个视野计数100个细胞，行阳性细胞数分级，0-1%=0，1-10%=1，10-50%=2，50-80%=3，80-100%=4）。两项评分乘积所得总分（IHS）进行结果判定：IHS0分为（-），IHS1~4分为（+），IHS5~8分为（++），IHS9~12分为（+++）。所有数据采用SPSS13.0统计软件处理。计数资料采用χ2（PearsonChi-Square Test）或Fish确切概率法；两组变量间的相关分析采用Spearman等级相关分析。所有检验均为双侧，P＜0.05为有统计学意义。 结果： 1正常宫颈组织、宫颈上皮内瘤变组织、宫颈癌组织中FR-α蛋白表达 正常宫颈组织、宫颈上皮内瘤变组织、宫颈癌组织中FR-α蛋白表达于细胞浆中，呈棕黄色颗粒。在本实验中，正常宫颈组织FR-α蛋白表达阳性率为6.7%，宫颈上皮内瘤变组织FR-α蛋白表达阳性率为76.2%，宫颈癌组织FR-α蛋白表达阳性率为81.7%，差异有统计学意义（P＜0.05），见table1。宫颈上皮内瘤变组织与正常组织中FR-α的表达阳性率相比，差异有统计学意义（P＜0.05），见table1。宫颈癌组织与宫颈上皮内瘤变组织中FR-α蛋白表达阳性率相比，差异无统计学意义（P0.05），见table1。 2不同病理类型中FR-α蛋白表达 CINI、CINII、CINIII中FR-α蛋白表达有差异，三者相比无统计学意义（P0.05）。见table2。宫颈癌I期、宫颈癌II期、宫颈癌III期蛋白表达有差异，三者差异无统计学意义（P0.05）。见Table3 3FR-α蛋白表达与宫颈癌危险因素的相关性 在宫颈癌组织及宫颈上皮内瘤变组织中，FR-α蛋白表达与年龄因素无关,年龄40与年龄≤40两组差别无统计学意义（P0.05），见Table4。在两组中，FR-α蛋白表达与HPV感染均有关,HPV感染阳性与HPV感染阴性两组差别有统计学意义（P0.05），见Table4。 4正常宫颈组织、宫颈上皮内瘤变组织、宫颈癌组织中Ki-67表达 正常宫颈组织、宫颈上皮内瘤变组织、宫颈癌组织中Ki-67表达于细胞核中，呈棕黄色颗粒。在正常宫颈组织中未见Ki-67表达（见Fig.4），宫颈上皮内瘤变组织及宫颈癌组织中Ki-67表达升高（见Fig.5,Fig.6），正常宫颈组织中Ki-67阳性率0%，宫颈上皮内瘤变组织中Ki-67阳性率71.4%，宫颈癌病变组织中Ki-67阳性率84.8%，三者差异有统计学意义(P＜0.05)。见table5，正常宫颈组织与宫颈上皮内瘤变组织中Ki-67蛋白表达阳性率相比，两者差异有统计学意义（P0.05）,宫颈上皮内瘤变组织与宫颈癌病变组织中Ki-67蛋白表达阳性率相比，两者差异无统计学意义（P0.05）。见Table5。 5不同病理类型中Ki-67表达 CINI、CINII、CINIII蛋白表达有差异，三者相比差异无统计学意义（P0.05）。见table6。宫颈癌I期、宫颈癌II期、宫颈癌III期Ki-67蛋白表达有差异，三者差异无统计学意义（P0.05），见Table7。 6Ki-67蛋白表达与宫颈癌危险因素的相关性 在宫颈癌及宫颈上皮内瘤变组织中，Ki-67蛋白表达与年龄因素无关，年龄40与年龄≤40两组差别无统计学意义（P0.05），见Table8。在两组中Ki-67蛋白表达与HPV感染无关，HPV感染阳性与HPV感染阴性两组差别无统计学意义（P0.05）,见Table8。 7宫颈上皮内瘤变组织及宫颈癌组织中FR-α蛋白表达与Ki-67的关系： 宫颈癌组织中二者呈正相关，相关系数r=0.532，p=0.000，有相关性，有统计学意义（P0.05)。宫颈上皮内瘤变组织中，FR-α蛋白表达与Ki-67蛋白表达呈正相关，相关系数r=0.504，p=0.003，有相关性，有统计学意义（P0.05） 结论： 1FR-α蛋白表达升高参与了宫颈癌发病。 2FR-α蛋白表达与年龄因素无关，与HPV感染有协同作用。 3Ki-67的高表达促进了肿瘤的发生，与HPV感染无协同作用。 4宫颈癌及宫颈上皮内瘤变组织中FR-α蛋白表达与Ki-67有相关性；FR-α蛋白可能通过影响细胞增殖参与宫颈癌的发生与发展。
[Abstract]:Objective : Cervical cancer ( cervical cancer ) is one of the most common gynecological malignant tumors , the second place in the malignant tumor of breast cancer , which is second only to breast cancer . Its pathological type is squamous cell carcinoma , adenocarcinoma , adenosquamous cell carcinoma . The reason of the disease is related to the following factors : 1 . High - risk HPV infection ;
2 . Sex and number of deliveries ;
3 . The infection plays a synergistic role in the infection of the pathogen such as chlamydia , herpes simplex virus type II , trichomonad , etc .
The folate receptor is a kind of membrane - binding protein which plays an important role in the process of cell metabolism , DNA synthesis and repair and the rapid proliferation and division of cancer cells . The folate receptor is a kind of membrane - binding protein .

Methods : The expression of FR - 伪 protein and the expression of Ki - 67 in normal cervical tissue , cervical epithelial neoplasia and cervical cancer were detected by immunohistochemical method . In the control group , 30 cases of normal cervical tissue , 42 cases of cervical intraepithelioma and 42 cases of positive expression were determined : brown - yellow granules appeared in the cytoplasm of the cells , and the results were determined by immunohistochemical method .
The percentage of positive cells was scored as percentage of positive cells : 5 visual fields were randomly selected , 100 cells were counted in each field of view , positive cell count was graded , 0 - 1 % = 0 , 1 - 10 % = 1 , 10 - 50 % = 2 , 50 - 80 % = 3 , 80 - 100 % = 4 ) . The results are as follows : ( - ) , ihs S1 - 4 are divided into ( + ) , ihs S5 - 8 are divided into ( ++ ) , ihs S9 ~ 12 are divided into ( ++ ) . Ki - 67 results are as follows : brown - yellow particles appear in the cytoplasm of the cells , and the results are determined by immunohistochemistry method . The results are as follows : no staining is 0 , light yellow is 1 , brown - yellow is 2 , brown - brown is 3 - point ;
The percentage of positive cells was scored as percentage of positive cells : 5 visual fields were randomly selected ( x 200 ) , 100 cells were counted in each field of view , the number of positive cells was graded , 0 - 1 % = 0 , 1 - 10 % = 1 , 10 - 50 % = 2 , 50 - 80 % = 3 , 80 - 100 % = 4 ) . The results were as follows : ( - ) , ihs S1 ~ 4 were divided into ( + ) , ihs S5 ~ 8 were divided into ( ++ ) , ihs S9 ~ 12 were divided into ( ++ ) . All the data were treated with SPSS 13.0 statistical software . The count data was analyzed by Pearsonchi - Square Test or Fish ' s exact probability method .
The correlation analysis between the two groups was analyzed by the correlation analysis between the two groups . All the tests were bilateral , P & lt ; 0.05 was statistically significant .

Results :

Expression of FR - 伪 in normal cervical tissue , cervical epithelial neoplasia and cervical cancer

In this experiment , the positive rate of FR - 伪 protein was 6.7 % , the positive rate of FR - 伪 protein was 76.2 % in normal cervical tissue , and the positive rate of FR - 伪 protein in cervical carcinoma was 81.7 % , and the difference was statistically significant ( P < 0.05 ) .

Expression of FR - 伪 protein in different pathological types

There was no significant difference in the expression of FR - 伪 protein in CINI , CINII and CINIII ( P0.05 ) .

Correlation between 3FR - 伪 protein expression and risk factors of cervical cancer

There was no significant difference between the expression of FR - 伪 protein and age in cervical cancer tissues and in cervical epithelial neoplasia . The difference between age 40 and age 鈮

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