Barrett食管患者临床、病理、内镜特征及病变粘膜DCAMKL-1蛋白表达的研究

发布时间：2018-07-20 11:05

【摘要】：Barrett食管(Barrett esophagus,BE)是指食管下段复层鳞状上皮由柱状上皮化生取代的病理现象,BE可经由“正常粘膜—柱状上皮化生—不典型增生(瘤变)—腺癌”途径恶变。而BE内镜及病理有不同分型与分级,并非所有类型都会进展为EA,各类型危险性也不同,可见早期诊断BE并明确其进展为EA的危险性,从而给予相应有效防治措施,能很大程度积极预防EA发生,极大改善生存和预后。DCAMKL-1是目前公认的胃肠道和腺癌干细胞标记物。在许多实体肿瘤内结缔组织间质部位出现DCAMKL-1表达上调现象,有研究显示其表达与恶变演变过程相关。本实验拟探索不同分型、分级BE间临床资料、病理表现间的差异以及免疫组织化学DCAMKL-1蛋白的表达情况,以期通过后者的特征差异及免疫组化临床应用的方便性、可行性助诊高危BE,积极预防EA发生。目的:研究BE患者不同临床分层数据,即性别、年龄、Gerd Q评分、饮食习惯、生活环境及经济能力等,与内镜下病变特征、病理分型与分级间的关系;探索DCAMKL-1在不同分型、分级BE及EA中表达有无差别。方法:采用四象限活检法、H.E.染色确诊BE。通过病理确定分型(胃型、肠型)及其分级(无瘤变、低级别瘤变、高级别瘤变)。对确诊BE者行胃食管反流病(GERD)问卷(Gerd Q)调查,总分≥8分诊断为GERD。对各BE患者行基本资料问卷调查,内容包括性别、年龄组(青中老年组)、饮食习惯(油咸辣、甜、清淡、不规律)、生活环境与经济能力(好中差)。统计胃镜下病变特征,包括分型(岛型、舌型、环周型、混合型)及所在象限、与齿状线距离、病变个数及大小等情况。另收集胃型和肠型中无瘤变、低级别瘤变、高级别瘤变及腺癌组织行DCAMKL-1免疫组织化学染色。结果1不同分型、分级BE临床基本资料的比较。31例BE患者中胃型26例,其中男性53.85%,女性46.15%,饮食油咸辣者73.08%,甜者11.54%,清淡者11.54%,不规律者3.84%,青年人26.92%,中年人53.85%,老年人19.23%,生活环境与经济能力差者3.84%,中等者84.62%,好者11.54%。肠型5例,其相应发生率分别为男性40.00%,女性60%,饮食油咸辣者80.00%,清淡者20.00%,中年人40.00%,老年人60.00%,全为生活环境与经济能力中等者。胃、肠型以上不同特征间比较差异均无统计学意义(P0.05)。而肠型中Gerd Q≥8分占80%,显著高于胃型的26.92%,差异有统计学意义(P=0.042,P0.05)。31例BE患者中无瘤变者共27例,低级别瘤变者4例,高级别瘤变者0例。其中无瘤变者中以上各项特征分别为51.85%,48.15%,70.37%,11.11%,14.81%,3.71%,37.04%,62.96%,18.52%,55.56%,25.92%,11.11%,85.19%,3.70%;低级别瘤变中分别为男性为50%,女性为50%,Gerd Q≥8分占25%,Gerd Q8分占75%,饮食全为油咸辣,青年人50%,中年人25.00%,老年人25.00%,生活环境与经济能力均为中等。可见无瘤变与低级别瘤变二者在以上特征的分布差异无统计学意义(P0.05)。2不同分型、分级BE临床基本资料的比较。31例BE中无瘤变胃型24例,在上述特征发生率分别为54.17%,45.83%,29.17%,70.83%,70.83%,12.50%,12.50%,4.17%,20.83%,58.34%,20.83%,12.50%,83.33%,4.17%;无瘤变肠型分别为33.33%,66.67%,全为Gerd Q≥8分,饮食油咸辣者66.67%,清淡者33.33%;中年人33.33%,老年人66.67%,全为生活环境与经济能力中等者;低级别瘤变胃型分别为男50%,女50%,全为Gerd Q8分,全为饮食油咸辣者,全为青年人,生活环境与经济能力全为中等。低级别瘤变肠型分别为男50%,女50%,Gerd Q≥8占50%,8占50%,饮食油咸辣者100%,中年人及老年人各50%,生活环境与经济能力均为中等。四种分型分级的以上特征分布差异无统计学意义(P0.05或P0.0083)。31例患者中无瘤变者共27例,其中胃型88.89%,肠型11.11%,低级别瘤变者共4例,其中胃型及肠型分别均为50%,其差异无统计学意义(P0.05)。3不同分型、分级BE胃镜下形态特征的比较。无瘤变者中岛型59.26%,舌型11.11%,环周型25.93%,混合型3.70%,低级别瘤变者共4例,岛型50%,舌型50%,环周型及混合型均为0%。差异无统计学意义(P0.05)。岛型共18例,其中无瘤变者16例,前壁12.5%,后壁12.5%,左壁62.5%,右壁12.5%,位于齿线上0~1 cm者43.75%,1~2 cm者56.25%,病变数为1处者占81.25%,2处以上者为18.75%,病变直径0.5 cm者占81.25%,≥0.5 cm者占18.75%;低级别瘤变者共2例,后壁和右壁各50%,均位于齿线上0~1 cm,病变数均为1处,病变直径均0.5 cm者。各特征间的差异无统计学意义(P0.05)。岛型又分为无瘤变胃型共14例,前壁14.29%,后壁14.29%,左壁57.13%,右壁14.29%,病变位于齿线上0~1 cm者42.86%,1~2 cm者57.14%,病变数为1处者78.57%,2处以上者21.43%,病变直径0.5 cm者92.86%,≥0.5 cm者7.14%。无瘤变肠型2例,均位于左壁,病变位于齿线上0~1 cm及1~2 cm者各50%,病变数均为1处,病变直径均≥0.5 cm。低级别瘤变胃型1例,位于后壁齿线上0~1 cm,病变数为1处,病变直径0.5 cm。低级别瘤变肠型1例,位于右壁齿线上0~1 cm,病变数为1处,病变直径0.5 cm。各分型分级间象限,距离齿线长度及病变个数及病变直径的差异无统计学意义(P0.05或P0.0083)。舌型共5例,其中无瘤变者3例,前壁66.67%,后壁33.33%,舌型均延伸于齿状线上长度≥3 cm,最宽≤1 cm者,等于2 cm者、3 cm者各33.33%、33.33%和33.34%;低级别瘤变者2例,前壁和后壁各50%,舌型延伸于齿状线上长度3 cm者和≥3 cm者各50%,最宽≤1 cm、2 cm各50%。各特征间的差异无统计学意义(P0.05)。舌型中,无瘤变胃型3例,前壁占66.67%,后壁占33.33%,病变延伸至齿线上≥3 cm者占100%,病变最宽处≤1 cm者、等于2 cm、3 cm者各33.33%。无瘤变肠型者0例。低级别瘤变胃型者1例,位于前壁,长度3 cm,最宽≤1 cm。低级别瘤变肠型者1例,位于后壁,长度≥3 cm,最宽为2 cm。各特征间差异无统计学意义(P0.05)。4不同分型、分级BE免疫组化DCAMKL-1表达的比较。对胃型无瘤变者、肠型无瘤变者、肠型低级别瘤变、肠型高级别瘤变,胃、肠型共存伴低级别瘤变及腺癌病理组织的DCAMKL-1免疫组化结果显示:各分型、分级BE均可见DCAMKL-1表达。其鳞状上皮细胞、化生上皮细胞及间质均有不同程度表达。胃型无瘤变者鳞状上皮内有少量表达,而较多表达于化生上皮细胞胞质内,间质中很少量表达。肠型无瘤变者鳞状上皮及间质及肠化生上皮内表达增加,以化生上皮及鳞状上皮内为著。二者细胞核的表达甚少。肠型低级别者,上述部位表达未见显著增加,但出现间质及化生上皮细胞核全核的表达。胃肠混合型伴低级别瘤变者,除鳞状细胞、化生上皮细胞及间质呈现表达较无瘤变者增多外,出现了化生细胞核表达进一步增高趋势,有意思的是还出现了化生细胞核核膜的特异性表达。肠型伴高级别瘤变者表现出鳞状细胞、间质表达的进一步升高,肠化生上皮细胞核表达增高,尤其是核膜表达显著增高。而腺癌组织呈现满视野表达的进一步增高,而未见核膜表达的突出增高。结论:1胃型更易伴随Gerd Q评分8的现象,而肠型患者更易伴随该评分≥8的现象,提示肠型患者比胃型患者更易伴随胃食管反流病,因此当胃镜下观察到胃食管反流病时应注意寻找有无BE,若发现BE应取活检加。Gerd Q评分系统作为BE危险性(肠型)的助诊可能有一定的价值。2其余各分型、分级间在基本资料及胃镜下形态特征方面均无统计学差异,尚不能依靠胃镜下形态观察确定病变危险性。3各分型、分级BE均可见DCAMKL-1表达。鳞状上皮内DCAMKL-1的表达随无瘤变、低级别瘤变、高级别瘤变及腺癌的顺序逐渐增多,无瘤变者间质表达很少,而伴有瘤变者出现明显间质表达,腺癌者表达更多,BE无瘤变者胃型及肠型均未见细胞核的显著表达,而低级别胃型、肠型均可见细胞核的明显表达,特别是胃肠混合型BE其化生细胞出现特异性核膜表达显著增加,而在高级别瘤变BE中核膜表达进一步增加,提示伴瘤变BE化生细胞核中DCAMKL-1的表达具有特异性,其表达的多少,尤其是核膜特异性表达甚至可以作为区分高级别瘤变与无瘤变者的手段,可能具有潜在助诊早期癌前病变的功能。
[Abstract]:Barrett Barrett esophagus (BE) is a pathological phenomenon in which the complex squamous epithelium of the lower segment of the esophagus is replaced by columnar epithelial metaplasia. BE can undergo malignant transformation via "normal mucosa columnar epitheliogenesis - atypical hyperplasia (tumorigenical) - adenocarcinoma." and BE endoscopy and pathology have different classification and classification. Not all types will advance to EA, and all types of BE The type of risk is also different. It can be seen that the early diagnosis of BE and the risk of its progression to EA, thus giving effective prevention and control measures, can proactively prevent the occurrence of EA and greatly improve the survival and prognosis of.DCAMKL-1, which is currently recognized as a marker of the gastrointestinal and adenocarcinoma stem cells. In many solid tumors, the interstitial sites of connective tissue appear DCA. The expression of MKL-1 is up-regulated, and some studies have shown that its expression is related to the evolution of malignant transformation. This experiment is to explore the clinical data of different typing, classification of BE, the difference between pathological manifestations and the expression of DCAMKL-1 protein in immunohistochemistry in order to make the diagnosis of the clinical application of the latter and the convenience of the clinical application of immunohistochemistry. High risk BE, active prevention of EA occurrence. Objective: To study the different clinical stratification data of BE patients, namely sex, age, Gerd Q score, diet habits, living environment and economic ability, and the relationship between pathological features of endoscopy, pathological classification and classification, and to explore the difference in the expression of DCAMKL-1 in different classifying, grading BE and EA. Methods: using four elephant limiting activities. The diagnosis of BE. was confirmed by H.E. staining (H.E.) and its classification (gastric type, intestinal type) and its classification (no tumor, low level of tumorigenicity, advanced tumor change). A total of more than 8 points were diagnosed as GERD. for the basic data of all BE patients, including sex, age group (middle-aged and old age group), and the total score of the total score was more than 8. Eating habits (oil salty, sweet, light, irregular), living environment and economic ability (good difference). Statistical gastroscopy pathological features, including classification (island type, tongue type, circumferential type, mixed type) and the quadrant, the distance from the dentate line, the number and size of the lesion, and the non tumor, low grade, high tumor and gland in the gastric and intestinal type The cancer tissue was stained with DCAMKL-1 immunohistochemical staining. Results 1 different classification and classification of BE clinical basic data in.31 cases, 26 cases of gastric type in BE patients, of which 53.85%, 46.15%, 73.08%, 11.54%, 11.54%, 3.84%, 26.92%, 53.85%, 19.23%, living environment and classics The poor ability was 3.84%, medium 84.62%, good 11.54%. enteric type 5 cases, the corresponding incidence rate was 40% for men, 60% for women, 80% in food oil, 20% in light, 40% in middle age and 60% in the elderly, and all of them were medium of living environment and economic ability. There was no statistical difference between the different characteristics of stomach and intestinal type (P0.05). In the intestinal type, Gerd Q more than 8 points accounted for 80%, significantly higher than the gastric type 26.92%, the difference was statistically significant (P=0.042, P0.05).31 cases of BE patients with no tumor in a total of 27 cases, 4 cases of low grade neoplasia and 0 cases of advanced tumor change. Among them, the above characteristics were 51.85%, 48.15%, 70.37%, 11.11%, 14.81%, 3.71%, 37.04%, 62.96%, etc. 25.92%, 11.11%, 85.19%, 3.70%. The low grade tumor was 50% for men, 50% for women, 25% for Gerd Q > 8, 75% in Gerd Q8, 50% in the youth, 50% in young people, 25% in middle-aged and 25% in the elderly. Statistical significance (P0.05).2 different typing, classification of BE clinical basic data comparison of.31 cases of BE without tumor gastric type, the incidence of the above characteristics were 54.17%, 45.83%, 29.17%, 70.83%, 70.83%, 12.50%, 12.50%, 4.17%, 20.83%, 58.34%, 20.83%, 12.50%, etc. 66.67% of oil and salt hot people, 33.33% for light, 33.33% in middle age and 66.67% in old people, all with moderate living environment and moderate economic ability; low grade tumor and stomach type were 50% men, 50% women, all Gerd Q8 points, all were young people, all were young, and the living environment and economic ability were all medium. The low grade intestinal type was 50%, 50%, Ger, respectively. D Q > 8 accounted for 50%, 8, 50%, 100%, middle-aged and aged 50%, both living environment and economic ability were medium. There were no statistical significance (P0.05 or P0.0083) among four types of classification and classification. There were 27 cases of.31 in.31 patients, including stomach 88.89%, intestinal type 11.11%, and low-grade tumorigenicity in 4 cases, of which gastric type was And the intestinal type were 50% respectively, and the difference was not statistically significant (P0.05).3 different typing, and the morphological characteristics of BE gastroscope were compared. The middle island type 59.26%, the tongue type 11.11%, the circumferential 25.93%, the mixed type 3.70%, the low grade tumor 4 cases, the island type 50%, the tongue type 50%, the circumferential type and the mixed type were all without statistical significance (P0.05). Of the 18 cases, there were 16 cases of no tumor, 12.5% of the anterior wall, 12.5% in the posterior wall, 62.5% in the left wall, 12.5% in the right wall, on the 0~1 cm in the tooth line 43.75%, the 1~2 cm in 56.25%, the number of the lesions in 81.25%, the 18.75% of more than 2, the lesion diameter 0.5 cm, or more than cm. 0~1 cm, the number of lesions were 1, the diameter of the lesions were 0.5 cm. The difference between the characteristics was not statistically significant (P0.05). The island type was divided into 14 cases without tumor, the anterior wall 14.29%, the posterior wall 14.29%, the left wall 57.13%, the right wall 14.29%, the lesion located on the 0~1 cm in the tooth line 42.86%, the 1~2 cm 57.14%, the pathological number 1 78.57%, 2 and more 21.43%, pathological lesions straight. Diameter 0.5 cm, 92.86%, or more than 0.5 cm, 7.14%. without tumor bowel type 2 cases, all located in the left wall, the lesion located on the tooth line 0~1 cm and 1~2 cm in 50%, the disease number is 1, the lesion diameter is equal to 0.5 cm. low grade tumor 1 cases, in the posterior wall tooth line 0~1 cm, the disease number is 1, 0.5 cm. low-grade and 0.5 cm. low-grade non tumor bowel type 1 cases, located in the right wall tooth line 0~1 cm, the number of lesions was 1, the diameter of the lesion was 0.5 cm., the difference between the length of the tooth line and the number of lesions and the diameter of the lesion was not statistically significant (P0.05 or P0.0083). There were 5 cases of tongue type, of which 3 cases were without tumor, 66.67% of the anterior wall, 33.33% of the posterior wall, and the tongue type extended to the length of the dentate line more than 3 cm, and the width was less than 1 cm, equal to 2 cm. The 3 cm were 33.33%, 33.33% and 33.34%, 2 cases in the lower grade and 50% in the anterior and posterior walls. The tongue type extended to 3 cm in the dentate line and 50% in the more than 3 cm, the width was less than 1 cm, and the difference between the characteristics of each 50%. was not statistically significant (P0.05). The non tumor gastric type 3 cases in the tongue type, the anterior wall occupy 66.67%, the posterior wall occupies 33.33%, and the lesion extends to the tooth line. Above 3 cm persons accounted for 100%, the width of the lesion was less than 1 cm, equal to 2 cm, 3 cm and 0 cases of 33.33%. without tumor intestinal type. 1 cases of low grade tumor and gastric type, located in the anterior wall, the length 3 cm, the width of less than 1 cm. low grade and 1 cases, the length more than 3 cm, the width of 2 cm. (P0.05).4 different classification, classification The comparison of the expression of DCAMKL-1 in BE immunohistochemistry. For the gastric type without tumor, the intestinal type without tumor, the intestinal type low grade change, the intestinal type advanced tumor change, the stomach, the intestinal type coexisting with the low grade tumor and the pathological tissue of the adenocarcinoma DCAMKL-1 immunohistochemical results showed that each classification, the graded BE can be seen in DCAMKL-1 expression. The interstitium was expressed in varying degrees. There was a small amount of expression in the squamous epithelium of the gastric carcinoma without tumor, but more expressed in the cytoplasm of the epithelial cells of the metaplasia and a small amount of expression in the interstitium. The expression of the squamous epithelium and the mesostroma and intestinal metaepithelia were increased in the intestinal type without tumor. The expression of the nucleus in the metaplasia and the squamous epithelium was very small. The expression of the nucleus was very little in the two cases. There was no significant increase in the expression of the above parts, but the expression of the nucleus and nucleus of the mesenchyme and metaplasia was found. The specific expression of the nuclear nuclear membrane of the metaplasia was presented. The intestinal type with high level of tumorigenicity showed the squamous cell, the increase of the expression of interstitial cells, the increase of the expression of the nucleus of the intestinal metaplasia, especially the expression of the nuclear membrane, while the adenocarcinoma tissue showed a further increase in the expression of the full field of vision, but no prominent increase in the expression of the nuclear membrane. 1 The gastric type is more likely to be accompanied by a Gerd Q score of 8, while the intestinal type is more likely to be associated with the score of more than 8, suggesting that the intestinal type patients are more likely to be accompanied by gastroesophageal reflux disease than the gastric type. Therefore, when the gastroesophageal reflux disease is observed under the gastroscope, the BE should be found. If the.Gerd Q scoring system should be taken as a BE risk (intestinal type), the BE should be found. There was a certain value of the value of.2, and there was no statistical difference between the basic data and the morphological features of the gastroscope. It was still not dependent on the morphological observation of the gastroscopy to determine the different types of risk.3, and the expression of DCAMKL-1 in the graded BE. The expression of DCAMKL-1 in the squamous epithelium with no tumor, low level of tumorigenicity and high grade The order of tumorigenicity and adenocarcinoma increased gradually. The expression of stroma in the non neoplasm was very few, but the expression of stroma in the tumor was obvious. The expression of the adenocarcinoma was more. The significant expression of the nucleus was not found in the gastric type and intestinal type of the BE without tumor, while the low grade gastric type and the intestinal type showed the obvious expression of the nucleus, especially the mixed BE of the gastrointestinal tract. The expression of the present specific nuclear membrane is significantly increased, and the expression of the nuclear membrane in the advanced tumor variant BE is further increased, suggesting that the expression of DCAMKL-1 in the BE nucleolus is specific. The expression of the nuclear membrane, especially the specific expression of the nuclear membrane, may even be used as a means to distinguish between the advanced tumor and the non tumor. Function of precancerous lesions.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R571

【参考文献】