Murakami Takashi, Yao Takashi, Mitomi Hiroyuki, Morimoto Takashi, Ueyama Hiroya, Matsumoto Kenshi, Saito Tsuyoshi, Osada Taro, Nagahara Akihito, Watanabe Sumio
Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
Department of Human Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
Gastric Cancer. 2016 Apr;19(2):498-507. doi: 10.1007/s10120-015-0497-9. Epub 2015 Apr 18.
Gastric adenocarcinoma with enteroblastic differentiation (GAED) has been recognized as a variant of alpha-fetoprotein (AFP)-producing gastric carcinoma, although its clinicopathologic and immunohistochemical features have not been fully elucidated.
To elucidate the clinicopathologic and immunohistochemical features of GAED, we analyzed 29 cases of GAED, including ten early and 19 advanced lesions, and compared these cases with 100 cases of conventional gastric adenocarcinoma (CGA). Immunohistochemistry for AFP, glypican 3, SALL4, and p53 was performed, and the phenotypic expression of the tumors was evaluated by immunostaining with antibodies against MUC5AC, MUC6, MUC2, CD10, and caudal-type homeobox 2 (CDX2).
Lymphatic and venous invasion was more frequent in GAED (76 and 72 %) than in CGA (41 and 31 %; P ≤ 0.001). Lymph node metastasis was more frequently observed in GAED (69 %) than in CGA (38 %; P = 0.005), as were synchronous or metachronous liver metastases (GAED, 31 %; CGA, 6 %; P ≤ 0.001). Immunohistochemically, all GAED were positive for at least one of three enteroblastic linage markers (AFP, glypican 3, and SALL4). Glypican 3 was the most sensitive marker (83 %) for GAED, followed by SALL4 (72 %) and AFP (45 %), whereas no CGA was positive. Furthermore, the rate of positive p53 staining was 59 % in GAED. Regarding the mucin phenotype, CD10 and CDX2 were diffusely or focally expressed in all GAED cases. Invasive areas with hepatoid or enteroblastic differentiation were negative for CD10 and CDX2.
Clinicopathologic features of GAED differ from those of CGA. GAED shows aggressive biological behavior, and is characteristically immunoreactive to AFP, glypican 3, or SALL4.
具有成肝细胞样分化的胃腺癌（GAED）已被认为是产生甲胎蛋白（AFP）的胃癌的一种变体，尽管其临床病理和免疫组化特征尚未完全阐明。
为阐明GAED的临床病理和免疫组化特征，我们分析了29例GAED病例，包括10例早期病变和19例进展期病变，并将这些病例与100例传统胃腺癌（CGA）进行比较。进行了AFP、磷脂酰肌醇蛋白聚糖3（glypican 3）、SALL4和p53的免疫组化检测，并用抗MUC5AC、MUC6、MUC2、CD10和尾型同源盒2（CDX2）抗体进行免疫染色评估肿瘤的表型表达。
GAED中淋巴管和静脉侵犯（分别为76%和72%）比CGA（分别为41%和31%；P≤0.001）更常见。GAED中淋巴结转移（69%）比CGA（38%；P = 0.005）更频繁，同时或异时性肝转移也是如此（GAED为31%，CGA为6%；P≤0.001）。免疫组化方面，所有GAED至少对三种成肝细胞样谱系标志物（AFP、glypican 3和SALL4）中的一种呈阳性。Glypican 3是GAED最敏感的标志物（83%），其次是SALL4（72%）和AFP（45%），而CGA均为阴性。此外，GAED中p53染色阳性率为59%。关于黏蛋白表型，CD10和CDX2在所有GAED病例中呈弥漫性或局灶性表达。具有肝样或成肝细胞样分化的浸润区域CD10和CDX2为阴性。
GAED的临床病理特征与CGA不同。GAED表现出侵袭性生物学行为，并且对AFP、glypican 3或SALL4具有特征性免疫反应性。
