Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Department of Pathology, Tata Memorial Centre, Mumbai, India.
J Clin Pathol. 2018 Mar;71(3):221-227. doi: 10.1136/jclinpath-2017-204535. Epub 2017 Aug 16.
This multi-institutional study and a re-evaluation of the TCGA cohort explores the morphological spectrum, genetics and outcome of GI (gastrointestinal) hepatoid tumours, tumours expressing alpha-fetoprotein (AFP) and fetal-type (FT) GI adenocarcinomas.
44 tumours with evidence of hepatocellular differentiation were evaluated for morphology as well as by immunohistochemistry for AFP, HepPar1, glypican-3 and arginase-1 and by in situ hybridisation for albumin. Three categories were defined: type I (hepatoid: morphological evidence of hepatocellular differentiation), type II (FT GI adenocarcinoma: tubular profiles and subnuclear vacuolisation, resembling fetal intestine) and type III: positive for at least two hepatocyte-specific markers but lacking morphological evidence of hepatocellular differentiation. GI adenocarcinomas in the TCGA cohort were also evaluated (n=829).
18 cases were classified as type I, 19 as FT GI adenocarcinomas and 7 as type III (resembling conventional gastrointestinal carcinomas). Serum AFP was elevated in 92% of cases. 93% of tumours were positive for glypican-3, 90% for albumin and 89% for AFP. Arginase-1 was restricted to 35% of type 1 tumours. TCGA gastric tumours with elevated AFP expression showed morphological features of FT GI adenocarcinoma (70%) and were exclusively MSI stable. TCGA gastric adenocarcinomas with high AFP expression showed inferior survival on univariate and multivariate analysis.
FT GI adenocarcinomas show a distinctive morphological and immunohistochemical profile. Gastric adenocarcinomas with elevated expression of AFP morphologically resemble FT GI adenocarcinomas, demonstrate aggressive behaviour, independent of grade and stage, and a distinct genetic profile.
本多机构研究和 TCGA 队列再评估旨在探索胃肠道（GI）肝样肿瘤、表达甲胎蛋白（AFP）和胎儿型（FT）GI 腺癌的形态学谱、遗传学和预后。
评估了 44 例具有肝细胞分化证据的肿瘤，评估内容包括形态学、免疫组织化学检测 AFP、HepPar1、glypican-3 和精氨酸酶-1，以及原位杂交检测白蛋白。定义了三个类别：I 型（肝样：具有肝细胞分化的形态学证据）、II 型（FT GI 腺癌：管状形态和核下空泡化，类似于胎儿肠道）和 III 型：至少两种肝细胞特异性标志物阳性，但缺乏肝细胞分化的形态学证据。还评估了 TCGA 队列中的 GI 腺癌（n=829）。
18 例被归类为 I 型，19 例为 FT GI 腺癌，7 例为 III 型（类似于常规胃肠道癌）。92%的病例血清 AFP 升高。93%的肿瘤对 glypican-3 呈阳性，90%对白蛋白呈阳性，89%对 AFP 呈阳性。精氨酸酶-1仅局限于 35%的 I 型肿瘤。TCGA 中 AFP 表达升高的胃肿瘤具有 FT GI 腺癌的形态特征（70%），且均为 MSI 稳定。TCGA 中 AFP 高表达的胃腺癌在单因素和多因素分析中显示出较差的生存结果。
FT GI 腺癌具有独特的形态学和免疫组织化学特征。AFP 表达升高的胃腺癌在形态上类似于 FT GI 腺癌，表现出侵袭性行为，独立于分级和分期，具有独特的遗传特征。
