Abstract：
Objective: To study the proportion and clinicopathological characteristics of gastric adenocarcinoma with enteroblastic differentiation (GAED) in gastric cancers showing an elevated serum alpha fetoprotein(AFP). Methods: A total of 724 resected gastric adenocarcinomas were collected from 2008 to 2018 at the 904 Hospital of Joint Service Support Force, and cases with pre-operative serum AFP>10 μg/L were screened. From the cases with elevated serum AFP, GAED cases were further evaluated based on morphology. Then the clincopathological features and immunohistochemical phenotypes of GAED were reviewed. In addition, the amplification of HER2 gene was detected with fluorescence in situ hybridization(FISH). When overall survival (OS) and progression-free survival (PFS) of GAED were analyzed, 289 cases ordinary gastric adenocarcinoma with normal serum AFP were employed as a control. Results: The percentage of GAED was 44% (11/25) in gastric cancers with elevated serum AFP. GAED was histologically tubular or papillary with clear cytoplasm, and some GAED cases showed cystadenoid structure similar to embryo sac (5 cases), homogeneous eosinophilic granules (4 cases) and intragland ulareosinophilic material (6 cases). All 11 GAED cases had lymph node metastasis. Liver metastasis and vascular thrombus were observed in 2 cases and 5 cases respectively. GAED was immunohistochemically positive for CDX2 (11/11), CD10 (8/11) and MUC2(3/11), which were intestinal epithelium differentiation markers. Meanwhile, primitive markers SALL4 (8/11), GPC3 (7/11) and AFP (5/11) were also expressed in GAED, and HER2 gene amplification was found in 3 cases (3/11) of GAED. Lastly, the PFS of GAED were significantly shorter than that of the control group (P=0.02), while OS was not statistically different between these two groups (P=0.99). Conclusions: Patients with GAED usually have a higher rate of elevated serum AFP in gastric adenocarcinoma, and the cancer exhibites features of both intestinal and primitive differentiation. As GAED is highly invasive, the prognosis of GAED may be poor. For GAED, the diagnosis of well-differentiated or moderately-differentiated adenocarcinoma should be avoided, because this diagnosis leads to underestimated malignant potential.
目的： 探讨血清甲胎蛋白（AFP）升高的胃癌病例中伴有肠母细胞分化的胃腺癌（GAED）所占比例及其临床病理特征。 方法： 收集2008至2018年解放军联勤保障部队第九○四医院胃癌手术切除标本共724例，以术前血清AFP>10 μg/L为标准，筛选血清AFP升高的胃癌病例，在此基础上按病理学标准筛选GAED病例，进一步观测其形态病理学特征，并采用免疫组织化学染色检测其分化表型，荧光原位杂交（FISH）检测HER2扩增情况。以289例不伴有AFP升高的普通胃腺癌作为对照组，比较GAED与对照组在无进展生存期和总体生存期上的差异。 结果： 724例胃腺癌中，伴血清AFP升高者有25例，其中GAED有11例，占44%。镜下观察：11例GAED以管状乳头状结构为主，胞质透明或空泡状，其中5例可见囊腺样结构，类似于胚胎发育时的胚囊；4例可见均质红染的圆形颗粒；6例可见腺腔内红染物。所有11例GAED均有淋巴结转移，同时2例有肝转移，5例可见血管内癌栓。癌细胞表达肠型分化标志物CDX2（11/11）、CD10（8/11）、MUC2（3/11）和原始分化标志物SALL4（8/11）、GPC3（7/11）、AFP（5/11）。同时有3例GAED存在HER2基因扩增（3/11）。随访显示，11例GAED的无进展生存期较对照组明显更短（P=0.02），而总体生存期则差异无统计学意义（P=0.99）。 结论： 导致血清AFP升高的胃癌中GAED占有较高比例，此类胃癌兼有肠型分化和原始的低分化特点，其侵袭转移能力强，预后可能较差，应避免将其诊断为普通高-中分化腺癌而低估其恶性程度。.
目的： 探讨血清甲胎蛋白（AFP）升高的胃癌病例中伴有肠母细胞分化的胃腺癌（GAED）所占比例及其临床病理特征。 方法： 收集2008至2018年解放军联勤保障部队第九○四医院胃癌手术切除标本共724例，以术前血清AFP>10 μg/L为标准，筛选血清AFP升高的胃癌病例，在此基础上按病理学标准筛选GAED病例，进一步观测其形态病理学特征，并采用免疫组织化学染色检测其分化表型，荧光原位杂交（FISH）检测HER2扩增情况。以289例不伴有AFP升高的普通胃腺癌作为对照组，比较GAED与对照组在无进展生存期和总体生存期上的差异。 结果： 724例胃腺癌中，伴血清AFP升高者有25例，其中GAED有11例，占44%。镜下观察：11例GAED以管状乳头状结构为主，胞质透明或空泡状，其中5例可见囊腺样结构，类似于胚胎发育时的胚囊；4例可见均质红染的圆形颗粒；6例可见腺腔内红染物。所有11例GAED均有淋巴结转移，同时2例有肝转移，5例可见血管内癌栓。癌细胞表达肠型分化标志物CDX2（11/11）、CD10（8/11）、MUC2（3/11）和原始分化标志物SALL4（8/11）、GPC3（7/11）、AFP（5/11）。同时有3例GAED存在HER2基因扩增（3/11）。随访显示，11例GAED的无进展生存期较对照组明显更短（P=0.02），而总体生存期则差异无统计学意义（P=0.99）。 结论： 导致血清AFP升高的胃癌中GAED占有较高比例，此类胃癌兼有肠型分化和原始的低分化特点，其侵袭转移能力强，预后可能较差，应避免将其诊断为普通高-中分化腺癌而低估其恶性程度。.
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