胃食管结合部早期癌胃肠表型标志物的表达及其临床意义

发布时间：2018-06-07 00:11

本文选题：胃食管结合部早期癌 + Siewert分型　；参考：《郑州大学》2017年硕士论文

【摘要】：1研究背景与目的Siewert将胃与食管连接部上下5 cm范围内发生的肿瘤定义为胃食管结合部(gastroesophageal junction,GEJ)肿瘤。GEJ肿瘤是胃肠道恶性肿瘤的一种亚型,其发病率在世界范围内呈上升趋势。在西方国家,GEJ腺癌的发病率已经超过了食管腺癌以及贲门腺癌。GEJ肿瘤的发病机制一直是临床及科研工作者困扰和关注的问题。进展期癌对癌周黏膜破坏较多,限制了对癌旁背景病变的认识;而早期癌病变处于初始阶段,其癌旁黏膜病理特征更具有代表性,能更好地反映肿瘤的起源、发生和发展过程。近年研究显示,国内Barrett食管发病率仍然很低,SiewertⅠ型腺癌并不多见。故本研究未将SiewertⅠ型纳入,仅研究SiewertⅡ型和Ⅲ型GEJ早期癌。本研究通过检测胃肠表型标志物的表达,并结合解剖学及癌周背景黏膜病变的组织学进行分析,拟探讨GEJ早期癌的临床病理特征。2材料和方法回顾性分析2010年4月至2015年7月确诊的53例GEJ早期癌(SiewertⅠ型、Ⅱ型和Ⅲ型),检测其胃肠表型标志物MUC5AC、MUC6、MUC2、CDX2和CD10的阳性表达,并根据免疫组织化学法结果将其分为胃型(G型)、胃肠型(GI型)、肠型(I型)和未分类型(NULL型),而后结合Siewert分型分析其临床病理特征。统计学分析采用卡方检验。3结果3.1 SiewertⅡ型和Ⅲ型GEJ早期癌胃肠表型标志物表达情况47例SiewertⅡ型和Ⅲ型GEJ早期癌患者的癌组织中,MUC5AC、MUC6、MUC2、CDX2和CD10的阳性表达者分别有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型者分别有11例(23.4%)、14例(29.8%)、21例(44.7%)和1例(2.1%)。在胃肠型中,MUC2的阳性表达明显高于CD10(92.9%/50.0%),差异有统计学意义(x2=4.375,P=0.036);肠型中,CDX2和MUC2的阳性表达明显高于CD10(85.7%/47.6%),差异有统计学意义(x2=9.956,P=0.007)。SiewertⅡ型的MUC5AC和MUC6阳性表达率分别为55.9%和50.0%,均高于SiewertⅢ型的15.4%;MUC2阳性表达率为55.9%,低于SiewertⅢ型的92.3%;差异均有统计学意义(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%,差异有统计学意义(x2=7.142,P=0.010)。3.2 SiewertⅡ型和Ⅲ型GEJ早期癌患者癌组织肿瘤黏液表型与临床病理特征的关系SiewertⅡ型和Ⅲ型GEJ早期癌患者的性别、组织学分型、浸润深度、肿瘤最大径在胃型、胃肠型和肠型中的分布差异均有统计学意义(P0.05)。肠型中男性所占比例高,分化良好型多,黏膜下层癌少,肿瘤最大径多小于胃型和胃肠型。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组织中,胃肠型和肠型的肠化生发生率分别为78.6%和81.0%,高于胃型的27.3%;胃肠型和肠型的腺体萎缩发生率分别为85.7%和85.7%,高于胃型的36.4%;差异均有统计学意义(Fisher确切概率法,P均0.05)。3.4 SiewertⅡ型和Ⅲ型GEJ进展期癌胃肠表型标志物表达情况在60例进展期癌中,MUC5AC、MUC6、MUC2、CDX2和CD10的表达分别为30例(50.0%),25例(41.7%),25例(41.7%),33例(55.0%),16例(26.7%);胃型,胃肠型,肠型和未分类型分别占19例(31.7%),23例(38.3%),15例(25.0%),3例(5.0%);在胃肠型中,CDX2的阳性表达明显高于CD10(82.6%/47.8%),差异有统计学意义(x2=6.133,P=0.029);在肠型中,CDX2的阳性表达明显高于CD10(93.3%/40.0%),差异有统计学意义(x2=9.600,P=0.009)。3.5 SiewertⅡ型和Ⅲ型GEJ进展期癌患者癌组织肿瘤黏液表型与临床病理特征的关系SiewertⅡ型和Ⅲ型GEJ进展癌患者的组织学分型、肿瘤最大径、远处转移的发生率在胃型、胃肠型和肠型中的分布差异均有统计学意义(P均0.05)。胃型中分化不良型多,肿瘤最大径多大于胃肠型和肠型,远处转移的发生率高。4结论4.1在GEJ癌进展过程中MUC2的表达呈减少趋势;MUC5AC和MUC6在SiewertⅡ型中的阳性表达率均高于SiewertⅢ型,而MUC2在SiewertⅡ型中的阳性表达率低于SiewertⅢ型,SiewertⅡ型中肠型所占比例低于SiewertⅢ型。4.2 SiewertⅡ、Ⅲ型GEJ早期癌以肠型多见,肠型中男性所占比例高,肠型肿瘤多分化良好,生长较慢,体积较小;SiewertⅡ、Ⅲ型GEJ进展期癌中肠型相对较少,其胃型多见分化不良型,且肿瘤较大,易发生远处转移。4.3在早期癌癌周背景黏膜组织中,胃肠型和肠型中肠化和萎缩的发生率明显高于胃型。4.4 SiewertⅡ、Ⅲ型GEJ早期癌可直接起源于胃型黏膜组织,恶性程度较高且进展较快;也可起源于胃肠型和肠型黏膜组织,癌变前存在萎缩和肠化生;4.5随着癌组织的进展,肠型可能会逐渐向胃型和(或)胃肠型转化。
[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.
【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】：R735

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