本文選題：胃食管結(jié)合部早期癌 + Siewert分型　； 參考：《鄭州大學(xué)》2017年碩士論文

【摘要】：1研究背景與目的Siewert將胃與食管連接部上下5 cm范圍內(nèi)發(fā)生的腫瘤定義為胃食管結(jié)合部(gastroesophageal junction,GEJ)腫瘤。GEJ腫瘤是胃腸道惡性腫瘤的一種亞型,其發(fā)病率在世界范圍內(nèi)呈上升趨勢。在西方國家,GEJ腺癌的發(fā)病率已經(jīng)超過了食管腺癌以及賁門腺癌。GEJ腫瘤的發(fā)病機(jī)制一直是臨床及科研工作者困擾和關(guān)注的問題。進(jìn)展期癌對癌周黏膜破壞較多,限制了對癌旁背景病變的認(rèn)識;而早期癌病變處于初始階段,其癌旁黏膜病理特征更具有代表性,能更好地反映腫瘤的起源、發(fā)生和發(fā)展過程。近年研究顯示,國內(nèi)Barrett食管發(fā)病率仍然很低,SiewertⅠ型腺癌并不多見。故本研究未將SiewertⅠ型納入,僅研究SiewertⅡ型和Ⅲ型GEJ早期癌。本研究通過檢測胃腸表型標(biāo)志物的表達(dá),并結(jié)合解剖學(xué)及癌周背景黏膜病變的組織學(xué)進(jìn)行分析,擬探討GEJ早期癌的臨床病理特征。2材料和方法回顧性分析2010年4月至2015年7月確診的53例GEJ早期癌(SiewertⅠ型、Ⅱ型和Ⅲ型),檢測其胃腸表型標(biāo)志物MUC5AC、MUC6、MUC2、CDX2和CD10的陽性表達(dá),并根據(jù)免疫組織化學(xué)法結(jié)果將其分為胃型(G型)、胃腸型(GI型)、腸型(I型)和未分類型(NULL型),而后結(jié)合Siewert分型分析其臨床病理特征。統(tǒng)計(jì)學(xué)分析采用卡方檢驗(yàn)。3結(jié)果3.1 SiewertⅡ型和Ⅲ型GEJ早期癌胃腸表型標(biāo)志物表達(dá)情況47例SiewertⅡ型和Ⅲ型GEJ早期癌患者的癌組織中,MUC5AC、MUC6、MUC2、CDX2和CD10的陽性表達(dá)者分別有21例(44.7%)、19例(40.4%)、31例(66.0%)、27例(57.4%)和17例(36.2%);G型、GI型、I型和NULL型者分別有11例(23.4%)、14例(29.8%)、21例(44.7%)和1例(2.1%)。在胃腸型中,MUC2的陽性表達(dá)明顯高于CD10(92.9%/50.0%),差異有統(tǒng)計(jì)學(xué)意義(x2=4.375,P=0.036);腸型中,CDX2和MUC2的陽性表達(dá)明顯高于CD10(85.7%/47.6%),差異有統(tǒng)計(jì)學(xué)意義(x2=9.956,P=0.007)。SiewertⅡ型的MUC5AC和MUC6陽性表達(dá)率分別為55.9%和50.0%,均高于SiewertⅢ型的15.4%;MUC2陽性表達(dá)率為55.9%,低于SiewertⅢ型的92.3%;差異均有統(tǒng)計(jì)學(xué)意義(x2=6.240、4.679、4.053,P均0.05)。SiewertⅡ型中I型占32.4%,低于SiewertⅢ型76.9%,差異有統(tǒng)計(jì)學(xué)意義(x2=7.142,P=0.010)。3.2 SiewertⅡ型和Ⅲ型GEJ早期癌患者癌組織腫瘤黏液表型與臨床病理特征的關(guān)系SiewertⅡ型和Ⅲ型GEJ早期癌患者的性別、組織學(xué)分型、浸潤深度、腫瘤最大徑在胃型、胃腸型和腸型中的分布差異均有統(tǒng)計(jì)學(xué)意義(P0.05)。腸型中男性所占比例高,分化良好型多,黏膜下層癌少,腫瘤最大徑多小于胃型和胃腸型。3.3 SiewertⅡ型和Ⅲ型GEJ早期癌的癌周背景黏膜分析在癌周背景黏膜組織中,胃腸型和腸型的腸化生發(fā)生率分別為78.6%和81.0%,高于胃型的27.3%;胃腸型和腸型的腺體萎縮發(fā)生率分別為85.7%和85.7%,高于胃型的36.4%;差異均有統(tǒng)計(jì)學(xué)意義(Fisher確切概率法,P均0.05)。3.4 SiewertⅡ型和Ⅲ型GEJ進(jìn)展期癌胃腸表型標(biāo)志物表達(dá)情況在60例進(jìn)展期癌中,MUC5AC、MUC6、MUC2、CDX2和CD10的表達(dá)分別為30例(50.0%),25例(41.7%),25例(41.7%),33例(55.0%),16例(26.7%);胃型,胃腸型,腸型和未分類型分別占19例(31.7%),23例(38.3%),15例(25.0%),3例(5.0%);在胃腸型中,CDX2的陽性表達(dá)明顯高于CD10(82.6%/47.8%),差異有統(tǒng)計(jì)學(xué)意義(x2=6.133,P=0.029);在腸型中,CDX2的陽性表達(dá)明顯高于CD10(93.3%/40.0%),差異有統(tǒng)計(jì)學(xué)意義(x2=9.600,P=0.009)。3.5 SiewertⅡ型和Ⅲ型GEJ進(jìn)展期癌患者癌組織腫瘤黏液表型與臨床病理特征的關(guān)系SiewertⅡ型和Ⅲ型GEJ進(jìn)展癌患者的組織學(xué)分型、腫瘤最大徑、遠(yuǎn)處轉(zhuǎn)移的發(fā)生率在胃型、胃腸型和腸型中的分布差異均有統(tǒng)計(jì)學(xué)意義(P均0.05)。胃型中分化不良型多,腫瘤最大徑多大于胃腸型和腸型,遠(yuǎn)處轉(zhuǎn)移的發(fā)生率高。4結(jié)論4.1在GEJ癌進(jìn)展過程中MUC2的表達(dá)呈減少趨勢;MUC5AC和MUC6在SiewertⅡ型中的陽性表達(dá)率均高于SiewertⅢ型,而MUC2在SiewertⅡ型中的陽性表達(dá)率低于SiewertⅢ型,SiewertⅡ型中腸型所占比例低于SiewertⅢ型。4.2 SiewertⅡ、Ⅲ型GEJ早期癌以腸型多見,腸型中男性所占比例高,腸型腫瘤多分化良好,生長較慢,體積較小;SiewertⅡ、Ⅲ型GEJ進(jìn)展期癌中腸型相對較少,其胃型多見分化不良型,且腫瘤較大,易發(fā)生遠(yuǎn)處轉(zhuǎn)移。4.3在早期癌癌周背景黏膜組織中,胃腸型和腸型中腸化和萎縮的發(fā)生率明顯高于胃型。4.4 SiewertⅡ、Ⅲ型GEJ早期癌可直接起源于胃型黏膜組織,惡性程度較高且進(jìn)展較快;也可起源于胃腸型和腸型黏膜組織,癌變前存在萎縮和腸化生;4.5隨著癌組織的進(jìn)展,腸型可能會逐漸向胃型和(或)胃腸型轉(zhuǎn)化。
[Abstract]:1 research background and objective Siewert defines the tumor occurring in the upper and lower 5 cm range of the gastric and esophageal junction as the gastroesophageal junction (GEJ) tumor.GEJ tumor is a subtype of gastrointestinal malignant tumor, and its incidence is on the rise worldwide. In western countries, the incidence of GEJ adenocarcinoma has been exceeded. The pathogenesis of adenocarcinoma of the esophagus and the adenocarcinoma of the cardia of the cardia has been a problem that has been plagued and concerned by the clinical and scientific researchers. The progressive cancer has more damage to the pericardial mucosa and restricts the understanding of the background lesions beside the cancer, while the early stage of the cancer is in the initial stage, and the characteristics of the paracancerous mucosa are more representative and can better reflect the swelling of the.GEJ. The origin, occurrence and development of the tumor. Recent studies have shown that the incidence of Barrett's esophagus is still very low in China, and Siewert type I adenocarcinoma is not common. Therefore, this study did not incorporate Siewert type I into the type of Siewert II and type III GEJ early cancer. The histology of membrane lesions was analyzed. A retrospective analysis of the clinicopathological features of GEJ early cancer was made by.2 materials and methods. A retrospective analysis of 53 early GEJ cases (type Siewert, type I, and type III) from April 2010 to July 2015 was used to detect the positive expression of MUC5AC, MUC6, MUC2, CDX2 and CD10 in the gastrointestinal phenotypes, and based on immunohistochemical staining. The results were divided into gastric (G), gastrointestinal (GI), intestinal type (type I) and undivided type (NULL type), and then combined with Siewert classification, the clinicopathological features were analyzed. Statistical analysis was conducted by chi square test of.3 results 3.1 Siewert II and type III GEJ early cancer gastrointestinal markers expression in 47 cases of early cancer patients with type Siewert II and type III GEJ. The positive expressions of MUC5AC, MUC6, MUC2, CDX2 and CD10 were 21 (44.7%), 19 (40.4%), 31 (66%), 27 (57.4%) and 17 (36.2%), and 11 (23.4%), 14, I and NULL (36.2%), GI, I and NULL. The positive expression of MUC2 was significantly higher than CD10 (92.9%/50.0%) in the gastrointestinal type. X2=4.375 (P=0.036), the positive expression of CDX2 and MUC2 in the intestinal type was significantly higher than that of CD10 (85.7%/47.6%). The difference was statistically significant (x2=9.956, P=0.007).Siewert II type MUC5AC and MUC6 positive expression rates were 55.9% and 50%, respectively higher than 15.4% of the Siewert type III, and the positive expression rate was 55.9%, which was lower than 92.3% of the type III type. The differences were statistically significant (x2=6.240,4.679,4.053, P 0.05).Siewert II type I 32.4%, lower than Siewert III type 76.9%, the difference was statistically significant (x2=7.142, P=0.010).3.2 Siewert II and type III GEJ early cancer tissue tumor mucus phenotype and clinicopathological features of Siewert type II and type III type GEJ early cancer patients There were significant differences in the distribution of gender, histological type, depth of infiltration, the maximum diameter of tumor in gastric, gastrointestinal and intestinal types (P0.05). The proportion of men in the intestinal type was high, the differentiation was good, the submucosa cancer was less, and the maximum diameter of the tumor was less than that of the gastric and gastrointestinal type.3.3 Siewert II and type III GEJ early cancer. The incidence of intestinal metaplasia in the gastrointestinal and intestinal types was 78.6% and 81%, respectively, 78.6% and 81%, higher than that of the gastric type, and the rate of gastrointestinal and intestinal type atrophy was 85.7% and 85.7%, respectively, higher than that of the gastric type, and the difference was statistically significant (Fisher ascertained probability, P 0.05).3.4 Siewert II and type III GEJ. The expression of MUC5AC, MUC6, MUC2, CDX2 and CD10 were expressed in 30 cases (50%), 25 (41.7%), 25 (41.7%), 33 (55%), 16 (26.7%), and gastric, gastrointestinal, and unclassified, respectively, respectively; in the gastrointestinal type, in the gastrointestinal type, CDX2 The positive expression was significantly higher than that of CD10 (82.6%/47.8%), the difference was statistically significant (x2=6.133, P=0.029), and the positive expression of CDX2 was significantly higher than that of CD10 (93.3%/40.0%) in the intestinal type (x2=9.600, P=0.009), and the relationship between the mucous phenotype and the clinicopathological features of the cancer tissue of the cancer tissue of the patients with.3.5 Siewert and type III GEJ progressing stage was statistically significant (x2=9.600, P=0.009). The histological classification, the maximum diameter of tumor and the incidence of distant metastasis in the patients with RT II and type III GEJ were statistically significant in the gastric, gastrointestinal and intestinal types (P 0.05). There were many dysplasia in the gastric type, the maximum diameter of the tumor was more than the gastrointestinal type and intestinal type, the incidence of distant metastasis was high.4 conclusion 4.1 in GEJ cancer. The expression of MUC2 in the course of MUC5AC and MUC6 in Siewert II was higher than that of Siewert III, but the positive expression rate of MUC2 in Siewert II was lower than that of Siewert III type, and the proportion of Siewert type middle intestinal type was lower than Siewert III.4.2 Siewert II. High differentiation, slower growth and smaller size of intestinal type tumor, Siewert II, type III type GEJ progressing carcinoma are relatively small in midgut type, and the gastric type is mostly poorly differentiated, and the tumor is larger, and the distant metastasis.4.3 is easily occurring in the early cancer peritumoral mucosa. The incidence of intestinal type and intestinal type and atrophy of intestinal type and intestinal type is significantly higher than that of the gastric type.4.4 S. Iewert II, type III GEJ early cancer can directly originate in gastric mucosa tissue, with high malignancy and rapid progress; it can also originate in gastrointestinal and intestinal mucosa tissues, and there is atrophy and intestinal metaplasia before canceration; 4.5 with the progress of cancer tissue, intestinal type may gradually transform into gastric and / or gastrointestinal type.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R735

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