E-cad和Fascin在伴MELF浸润子宫内膜样癌诊断中的应用研究

发布时间：2018-06-10 04:14

本文选题：子宫内膜样癌 + MELF浸润　；参考：《郑州大学》2017年硕士论文

【摘要】：背景与目的子宫内膜癌是最常见的女性生殖系统恶性肿瘤之一。近年来,子宫内膜癌的发病率明显上升,且有年轻化的趋势,严重威胁我国女性健康。基于不同的起源、临床病理表现和遗传学特征将子宫内膜癌分为Ⅰ型和Ⅱ型。子宫内膜样癌是子宫内膜癌中最常见的类型,属于Ⅰ型子宫内膜癌,其预后较好。近年来病理学界发现子宫内膜癌中存在一种罕见的特殊浸润方式;即MELF(microcystic elongated and fragmented)浸润。经研究证实其仅发生于子宫内膜样腺癌这一组织学类型中。文献报道其仅发生于低级别、伴有肌层浸润的子宫内膜样癌中。可发生于任一临床分期。目前国内外报道一致认为伴有这种特殊浸润方式的子宫内膜癌具有较高的淋巴结转移率且临床预后较差。因此,伴有MELF浸润的内膜癌的正确诊断尤为重要,对指导临床治疗以及患者预后提供重要的意义。该病变的诊断主要依据HE染色镜下观察进行判别,MELF浸润方式仅位于子宫肌间,可与内膜样腺癌腺体连续存在或局灶浸润于肌层。其发生较为隐匿,仅凭HE组织形态学镜下观察容易漏诊。另外其和肌间脉管及其他组织易混淆,仅凭HE组织形态学有误诊的可能。因此,有必要采用免疫组化进行辅助诊断。目前辅助诊断子宫内膜癌常见的免疫组化指标:CK、CK7、ER、PR、Vimentin、P16、Ki-67等。根据文献报道的辅助诊断MELF浸润的免疫组化方法中,CK7能更特异地辅助诊断MELF浸润。因此,在伴有高度疑似MELF浸润的子宫内膜样癌病例中可应用CK7辅助诊断。但其效果不能完全令人满意,因此寻找新的辅助诊断MELF的新指标为当务之急。此外,关于MELF的基础研究中发现:肌动蛋白结合蛋白(Fascin)在正常细胞和肿瘤细胞中均可表达。其表达上调与肿瘤细胞侵袭性增加有着密切关系。上皮性钙黏蛋白(E-cadherin)是一种细胞黏附蛋白,在介导同类细胞间黏附、细胞信号转导中起到一定作用。E-cad失表达或低表达是肿瘤发生侵袭和远处转移最重要的机制之一。现补做二者可能与MELF浸润的关系研究。本研究采用免疫组化方法对23例疑似MELF浸润的子宫内膜样癌组织中E-cad、Fascin表达进行检测及临床病理学分析,并探讨二者在诊断MELF浸润中的作用。方法收集2011年01月-2015年01月间郑州大学第一附属医院经全子宫切除术确诊的子宫内膜样癌病例140例。依据文献报道的MELF浸润的诊断标准进行筛选,最终发现伴有疑似MELF浸润病例23例。年龄介于45岁-70岁之间,平均年龄58.3岁。实验运用免疫组化方法检测E-cad、Fascin的蛋白表达,并对上述方法进行比较分析。探讨其对伴有MELF浸润的子宫内膜样癌进行辅助诊断的可能性。应用SPSS 17.0进行数据分析,定性资料率的比较采用χ2检验,检验水准α=0.05。结果1、23例疑似MELF浸润CK7结果:其中有8例呈弥漫均一强阳性,其周围内膜样癌腺体阳性强度不一,多为弱阳性或阴性。结合组织形态学诊断为MELF浸润。故本研究中其发生率为5.71%(8/140)。2、23例疑似MELF浸润E-cad结果:其中有15例呈不连续弱阳性,其周围内膜样癌腺体多呈均一、完整的基底膜的染色,少数呈局灶阳性。结合组织形态学诊断为MELF浸润。3、23例疑似MELF浸润Fascin结果:其中有11例呈阳性,其周围反应性间质及间质小血管均呈阳性、周围内膜样癌腺体呈阴性或灶阳性。4、E-cad、Fascin及联合二者在诊断MELF浸润统计学结果:E-cad与CK7在MELF浸润的检出率上有统计学差异(P0.05)。Fascin与CK7在MELF浸润的检出率上无统计学差异(P0.05)。联合应用E-cad和Fascin与CK7对MELF浸润的检出率上无统计学差异(P0.05)。5、三种方法准确率的比较结果:E-cad和Fascin联合用于诊断MELF浸润结果的符合率(78.26%)高于单独使用E-cad(69.57%)和Fascin(60.87%)时诊断的符合率。且在本实验中单独应用Fascin(60.87%)对MELF浸润诊断的符合率较单独应用E-cad(69.57%)低。E-cad、Fascin和联合二者这三组对诊断MELF浸润符合率(准确度)之间无统计学差异(P0.05)。结论1、E-cad和Fascin可作为辅助诊断子宫内膜样癌伴MELF浸润,但明确诊断还需结合组织学形态,联合二者效果更佳。
[Abstract]:Background and objective endometrial carcinoma is one of the most common malignant tumor of female reproductive system. In recent years, the incidence of endometrial cancer has increased significantly and has a tendency to be young. It is a serious threat to the health of women in China. Endometrial carcinoma is divided into type I and type II Types Based on different origins, clinicopathological and genetic features. Endometrium endometrium is divided into endometrium type I and type II. Carcinoma of the endometrium is the most common type of endometrial carcinoma and belongs to type I endometrial carcinoma. It has a better prognosis. In recent years, there is a rare special invasive method in endometrial carcinoma, that is, MELF (microcystic elongated and fragmented) infiltration. It is reported that it occurs only in low grade, myometrium infiltrating endometrioid carcinoma. It can occur at any clinical stage. It is reported that endometrial cancer with this special invasive method has high lymph node metastasis rate and poor clinical prognosis. Therefore, the diagnosis of endometrial carcinoma with MELF infiltration is being confirmed. It is of particular importance to guide clinical treatment and patient prognosis. The diagnosis of this lesion is mainly based on the observation of HE staining. The mode of MELF infiltration is located only in the intermyometrium of the uterus. It can continue to exist or infiltrate into the myometrium with endometrioid adenocarcinoma glands. The onset of the disease is more concealed, only under the HE histomorphology. It is easy to misdiagnose. Besides, it is easily confused with the intermuscular pulse tube and other tissues. It is possible only by HE histomorphology. Therefore, it is necessary to use immunohistochemical method for auxiliary diagnosis. At present, the common immunohistochemical indexes of endometrial carcinoma are diagnosed as CK, CK7, ER, PR, Vimentin, P16, Ki-67, etc. according to the auxiliary diagnosis of the literature. In immunohistochemical methods, CK7 can more specifically assist in the diagnosis of MELF infiltration. Therefore, CK7 assisted diagnosis can be used in cases of endometrioid carcinoma with highly suspected MELF infiltration. But the effect can not be completely satisfactory. Therefore, it is urgent to find a new indicator of the new auxiliary diagnostic MELF. In addition, the basic study on MELF has been found: Actin binding protein (Fascin) can be expressed in normal and tumor cells. The up-regulated expression is closely related to the increase of tumor cell invasiveness. Epithelial calcin (E-cadherin) is a cell adhesion protein that mediates the adhesion between the same cells, and the cell signaling transduction plays a role in.E-cad loss of expression or low expression. It is one of the most important mechanisms of tumor invasion and distant metastasis. The relationship between the two and the MELF infiltration may be studied. The immunohistochemical method was used to examine the expression of E-cad and Fascin in 23 cases of endometrioid carcinoma suspected to be infiltrated, and to analyze the clinical pathology, and to explore the two cases in the diagnosis of MELF infiltration. Methods to collect 140 cases of endometrioid carcinoma diagnosed by total hysterectomy in the First Affiliated Hospital of Zhengzhou University from 01 months of -2015 2011 to 01 months. According to the diagnostic criteria of MELF infiltration reported in the literature, 23 cases with suspected MELF infiltration were found, between the age of 45 and the age of 58.3 years. The average age was 58.3 years old. The protein expression of E-cad and Fascin was detected by immunohistochemical method, and the possibility of the auxiliary diagnosis of endometrioid carcinoma with MELF infiltration was analyzed. The data analysis was carried out with SPSS 17. The comparison of the qualitative data rate using the chi 2 test was used to test the level of alpha =0.05. results of 1,23 cases suspected to be MELF infiltrating CK7. Results: there were 8 cases of diffuse homogeneous strong positive. The positive intensity of endometrioid carcinoma in the surrounding area was not one, mostly weak positive or negative. The diagnosis of MELF infiltration with histomorphology was 5.71% (8/140).2,23 cases suspected of MELF infiltration in E-cad: 15 of them were discontinuous and weak positive, and the surrounding endometrioid carcinoma gland More homogeneous, complete basilar membrane staining, a small number of local focal positive. Combined with histomorphology, MELF infiltrated.3,23 cases suspected MELF infiltration Fascin results: 11 cases were positive, the peripheral reactive interstitial and interstitial small blood vessels were positive, peripheral endometrioid carcinoma glands were negative or.4, E-cad, Fascin and combined two were in the positive. There was no statistical difference between the detection rate of E-cad and CK7 in the infiltration of MELF (P0.05), there was no statistical difference between.Fascin and CK7 in the infiltration of MELF (P0.05). There was no statistical difference in the detection rate of the infiltration between E-cad and Fascin and CK7. The results of the three methods of accuracy were compared with those of the three methods. The coincidence rate of CIN combined with the diagnosis of MELF infiltration (78.26%) was higher than that of E-cad (69.57%) and Fascin (60.87%). In this experiment, the coincidence rate of Fascin (60.87%) for MELF infiltration diagnosis was lower than that of E-cad (69.57%), Fascin and two of the three groups for the diagnosis of MELF. There is no statistical difference between accuracy (P0.05). Conclusion 1, E-cad and Fascin can be used as an auxiliary diagnosis for endometrioid carcinoma with MELF infiltration, but a definite diagnosis should be combined with histological morphology, and the combined effect of the combined two is better.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.33

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