【摘要】：Barrett食管(Barrett esophagus,BE)是指食管下段復(fù)層鱗狀上皮由柱狀上皮化生取代的病理現(xiàn)象,BE可經(jīng)由“正常粘膜—柱狀上皮化生—不典型增生(瘤變)—腺癌”途徑惡變。而B(niǎo)E內(nèi)鏡及病理有不同分型與分級(jí),并非所有類(lèi)型都會(huì)進(jìn)展為EA,各類(lèi)型危險(xiǎn)性也不同,可見(jiàn)早期診斷BE并明確其進(jìn)展為EA的危險(xiǎn)性,從而給予相應(yīng)有效防治措施,能很大程度積極預(yù)防EA發(fā)生,極大改善生存和預(yù)后。DCAMKL-1是目前公認(rèn)的胃腸道和腺癌干細(xì)胞標(biāo)記物。在許多實(shí)體腫瘤內(nèi)結(jié)締組織間質(zhì)部位出現(xiàn)DCAMKL-1表達(dá)上調(diào)現(xiàn)象,有研究顯示其表達(dá)與惡變演變過(guò)程相關(guān)。本實(shí)驗(yàn)擬探索不同分型、分級(jí)BE間臨床資料、病理表現(xiàn)間的差異以及免疫組織化學(xué)DCAMKL-1蛋白的表達(dá)情況,以期通過(guò)后者的特征差異及免疫組化臨床應(yīng)用的方便性、可行性助診高危BE,積極預(yù)防EA發(fā)生。目的:研究BE患者不同臨床分層數(shù)據(jù),即性別、年齡、Gerd Q評(píng)分、飲食習(xí)慣、生活環(huán)境及經(jīng)濟(jì)能力等,與內(nèi)鏡下病變特征、病理分型與分級(jí)間的關(guān)系;探索DCAMKL-1在不同分型、分級(jí)BE及EA中表達(dá)有無(wú)差別。方法:采用四象限活檢法、H.E.染色確診BE。通過(guò)病理確定分型(胃型、腸型)及其分級(jí)(無(wú)瘤變、低級(jí)別瘤變、高級(jí)別瘤變)。對(duì)確診BE者行胃食管反流病(GERD)問(wèn)卷(Gerd Q)調(diào)查,總分≥8分診斷為GERD。對(duì)各BE患者行基本資料問(wèn)卷調(diào)查,內(nèi)容包括性別、年齡組(青中老年組)、飲食習(xí)慣(油咸辣、甜、清淡、不規(guī)律)、生活環(huán)境與經(jīng)濟(jì)能力(好中差)。統(tǒng)計(jì)胃鏡下病變特征,包括分型(島型、舌型、環(huán)周型、混合型)及所在象限、與齒狀線(xiàn)距離、病變個(gè)數(shù)及大小等情況。另收集胃型和腸型中無(wú)瘤變、低級(jí)別瘤變、高級(jí)別瘤變及腺癌組織行DCAMKL-1免疫組織化學(xué)染色。結(jié)果1不同分型、分級(jí)BE臨床基本資料的比較。31例BE患者中胃型26例,其中男性53.85%,女性46.15%,飲食油咸辣者73.08%,甜者11.54%,清淡者11.54%,不規(guī)律者3.84%,青年人26.92%,中年人53.85%,老年人19.23%,生活環(huán)境與經(jīng)濟(jì)能力差者3.84%,中等者84.62%,好者11.54%。腸型5例,其相應(yīng)發(fā)生率分別為男性40.00%,女性60%,飲食油咸辣者80.00%,清淡者20.00%,中年人40.00%,老年人60.00%,全為生活環(huán)境與經(jīng)濟(jì)能力中等者。胃、腸型以上不同特征間比較差異均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。而腸型中Gerd Q≥8分占80%,顯著高于胃型的26.92%,差異有統(tǒng)計(jì)學(xué)意義(P=0.042,P0.05)。31例BE患者中無(wú)瘤變者共27例,低級(jí)別瘤變者4例,高級(jí)別瘤變者0例。其中無(wú)瘤變者中以上各項(xiàng)特征分別為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%;低級(jí)別瘤變中分別為男性為50%,女性為50%,Gerd Q≥8分占25%,Gerd Q8分占75%,飲食全為油咸辣,青年人50%,中年人25.00%,老年人25.00%,生活環(huán)境與經(jīng)濟(jì)能力均為中等�？梢�(jiàn)無(wú)瘤變與低級(jí)別瘤變二者在以上特征的分布差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。2不同分型、分級(jí)BE臨床基本資料的比較。31例BE中無(wú)瘤變胃型24例,在上述特征發(fā)生率分別為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%;無(wú)瘤變腸型分別為33.33%,66.67%,全為Gerd Q≥8分,飲食油咸辣者66.67%,清淡者33.33%;中年人33.33%,老年人66.67%,全為生活環(huán)境與經(jīng)濟(jì)能力中等者;低級(jí)別瘤變胃型分別為男50%,女50%,全為Gerd Q8分,全為飲食油咸辣者,全為青年人,生活環(huán)境與經(jīng)濟(jì)能力全為中等。低級(jí)別瘤變腸型分別為男50%,女50%,Gerd Q≥8占50%,8占50%,飲食油咸辣者100%,中年人及老年人各50%,生活環(huán)境與經(jīng)濟(jì)能力均為中等。四種分型分級(jí)的以上特征分布差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05或P0.0083)。31例患者中無(wú)瘤變者共27例,其中胃型88.89%,腸型11.11%,低級(jí)別瘤變者共4例,其中胃型及腸型分別均為50%,其差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。3不同分型、分級(jí)BE胃鏡下形態(tài)特征的比較。無(wú)瘤變者中島型59.26%,舌型11.11%,環(huán)周型25.93%,混合型3.70%,低級(jí)別瘤變者共4例,島型50%,舌型50%,環(huán)周型及混合型均為0%。差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。島型共18例,其中無(wú)瘤變者16例,前壁12.5%,后壁12.5%,左壁62.5%,右壁12.5%,位于齒線(xiàn)上0~1 cm者43.75%,1~2 cm者56.25%,病變數(shù)為1處者占81.25%,2處以上者為18.75%,病變直徑0.5 cm者占81.25%,≥0.5 cm者占18.75%;低級(jí)別瘤變者共2例,后壁和右壁各50%,均位于齒線(xiàn)上0~1 cm,病變數(shù)均為1處,病變直徑均0.5 cm者。各特征間的差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。島型又分為無(wú)瘤變胃型共14例,前壁14.29%,后壁14.29%,左壁57.13%,右壁14.29%,病變位于齒線(xiàn)上0~1 cm者42.86%,1~2 cm者57.14%,病變數(shù)為1處者78.57%,2處以上者21.43%,病變直徑0.5 cm者92.86%,≥0.5 cm者7.14%。無(wú)瘤變腸型2例,均位于左壁,病變位于齒線(xiàn)上0~1 cm及1~2 cm者各50%,病變數(shù)均為1處,病變直徑均≥0.5 cm。低級(jí)別瘤變胃型1例,位于后壁齒線(xiàn)上0~1 cm,病變數(shù)為1處,病變直徑0.5 cm。低級(jí)別瘤變腸型1例,位于右壁齒線(xiàn)上0~1 cm,病變數(shù)為1處,病變直徑0.5 cm。各分型分級(jí)間象限,距離齒線(xiàn)長(zhǎng)度及病變個(gè)數(shù)及病變直徑的差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05或P0.0083)。舌型共5例,其中無(wú)瘤變者3例,前壁66.67%,后壁33.33%,舌型均延伸于齒狀線(xiàn)上長(zhǎng)度≥3 cm,最寬≤1 cm者,等于2 cm者、3 cm者各33.33%、33.33%和33.34%;低級(jí)別瘤變者2例,前壁和后壁各50%,舌型延伸于齒狀線(xiàn)上長(zhǎng)度3 cm者和≥3 cm者各50%,最寬≤1 cm、2 cm各50%。各特征間的差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。舌型中,無(wú)瘤變胃型3例,前壁占66.67%,后壁占33.33%,病變延伸至齒線(xiàn)上≥3 cm者占100%,病變最寬處≤1 cm者、等于2 cm、3 cm者各33.33%。無(wú)瘤變腸型者0例。低級(jí)別瘤變胃型者1例,位于前壁,長(zhǎng)度3 cm,最寬≤1 cm。低級(jí)別瘤變腸型者1例,位于后壁,長(zhǎng)度≥3 cm,最寬為2 cm。各特征間差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。4不同分型、分級(jí)BE免疫組化DCAMKL-1表達(dá)的比較。對(duì)胃型無(wú)瘤變者、腸型無(wú)瘤變者、腸型低級(jí)別瘤變、腸型高級(jí)別瘤變,胃、腸型共存伴低級(jí)別瘤變及腺癌病理組織的DCAMKL-1免疫組化結(jié)果顯示:各分型、分級(jí)BE均可見(jiàn)DCAMKL-1表達(dá)。其鱗狀上皮細(xì)胞、化生上皮細(xì)胞及間質(zhì)均有不同程度表達(dá)。胃型無(wú)瘤變者鱗狀上皮內(nèi)有少量表達(dá),而較多表達(dá)于化生上皮細(xì)胞胞質(zhì)內(nèi),間質(zhì)中很少量表達(dá)。腸型無(wú)瘤變者鱗狀上皮及間質(zhì)及腸化生上皮內(nèi)表達(dá)增加,以化生上皮及鱗狀上皮內(nèi)為著。二者細(xì)胞核的表達(dá)甚少。腸型低級(jí)別者,上述部位表達(dá)未見(jiàn)顯著增加,但出現(xiàn)間質(zhì)及化生上皮細(xì)胞核全核的表達(dá)。胃腸混合型伴低級(jí)別瘤變者,除鱗狀細(xì)胞、化生上皮細(xì)胞及間質(zhì)呈現(xiàn)表達(dá)較無(wú)瘤變者增多外,出現(xiàn)了化生細(xì)胞核表達(dá)進(jìn)一步增高趨勢(shì),有意思的是還出現(xiàn)了化生細(xì)胞核核膜的特異性表達(dá)。腸型伴高級(jí)別瘤變者表現(xiàn)出鱗狀細(xì)胞、間質(zhì)表達(dá)的進(jìn)一步升高,腸化生上皮細(xì)胞核表達(dá)增高,尤其是核膜表達(dá)顯著增高。而腺癌組織呈現(xiàn)滿(mǎn)視野表達(dá)的進(jìn)一步增高,而未見(jiàn)核膜表達(dá)的突出增高。結(jié)論:1胃型更易伴隨Gerd Q評(píng)分8的現(xiàn)象,而腸型患者更易伴隨該評(píng)分≥8的現(xiàn)象,提示腸型患者比胃型患者更易伴隨胃食管反流病,因此當(dāng)胃鏡下觀察到胃食管反流病時(shí)應(yīng)注意尋找有無(wú)BE,若發(fā)現(xiàn)BE應(yīng)取活檢加。Gerd Q評(píng)分系統(tǒng)作為BE危險(xiǎn)性(腸型)的助診可能有一定的價(jià)值。2其余各分型、分級(jí)間在基本資料及胃鏡下形態(tài)特征方面均無(wú)統(tǒng)計(jì)學(xué)差異,尚不能依靠胃鏡下形態(tài)觀察確定病變危險(xiǎn)性。3各分型、分級(jí)BE均可見(jiàn)DCAMKL-1表達(dá)。鱗狀上皮內(nèi)DCAMKL-1的表達(dá)隨無(wú)瘤變、低級(jí)別瘤變、高級(jí)別瘤變及腺癌的順序逐漸增多,無(wú)瘤變者間質(zhì)表達(dá)很少,而伴有瘤變者出現(xiàn)明顯間質(zhì)表達(dá),腺癌者表達(dá)更多,BE無(wú)瘤變者胃型及腸型均未見(jiàn)細(xì)胞核的顯著表達(dá),而低級(jí)別胃型、腸型均可見(jiàn)細(xì)胞核的明顯表達(dá),特別是胃腸混合型BE其化生細(xì)胞出現(xiàn)特異性核膜表達(dá)顯著增加,而在高級(jí)別瘤變BE中核膜表達(dá)進(jìn)一步增加,提示伴瘤變BE化生細(xì)胞核中DCAMKL-1的表達(dá)具有特異性,其表達(dá)的多少,尤其是核膜特異性表達(dá)甚至可以作為區(qū)分高級(jí)別瘤變與無(wú)瘤變者的手段,可能具有潛在助診早期癌前病變的功能。
[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.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類(lèi)號(hào)】：R571

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相關(guān)期刊論文 前4條

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本文編號(hào)：2133321