Abstract：
Hepatoid or α-fetoprotein (AFP)-producing adenocarcinomas of stomach growing in a solid pattern are highly aggressive tumors. It is difficult to detect hepatoid differentiation solely based on findings from hematoxylin and eosin stainings, especially in small biopsy specimens. Gastric adenocarcinomas with hepatoid differentiation should be distinguished from solid-type gastric adenocarcinoma because of their different biological behavior. We immunohistochemically analyzed hepatocellular markers (AFP, glypican 3, and Hepatocyte paraffin 1 [HepPar-1]) and possible markers of gastric hepatoid adenocarcinoma (Sal-like protein 4 [SALL4] and palate, lung, and nasal epithelium carcinoma-associated protein [PLUNC]) to detect hepatoid differentiation in 45 gastric hepatoid adenocarcinomas and 47 nonhepatoid solid-type poorly differentiated adenocarcinomas. There were a higher incidence of vascular invasion (P = .0055) and distant metastasis (P = .0458) in hepatoid adenocarcinoma than in nonhepatoid adenocarcinoma. AFP, SALL4, HepPar-1, and glypican 3 were significantly higher in hepatoid adenocarcinoma than in nonhepatoid adenocarcinoma. All 5 markers were positive in both the hepatoid/solid and the tubular component. In hepatoid adenocarcinoma, the frequency of distant metastasis was significantly higher in SALL4-negative cases than in SALL4-positive cases (P = .0381). HepPar-1 was associated with liver metastasis (P = .0452). PLUNC was correlated with lymph node metastasis (P = .0375). There was a significant difference in the survival rate between HepPar-1-positive and HepPar-1-negative groups (P = .0437). The coexpression of PLUNC and SALL4 and the other coexpression of HepPar-1 and PLUNC were associated with poorer prognosis (P = .0181 and P = .0443, respectively). AFP, SALL4, HepPar-1, and glypican 3 are useful for the detection of hepatoid differentiation. A combination of PLUNC, HepPar-1, and SALL4 could be a reliable prognostic indicator in hepatoid adenocarcinoma of the stomach.
摘要：
产生肝样或甲胎蛋白（AFP）的胃癌以固体模式生长是高度侵袭性的肿瘤。仅根据苏木精和曙红染色的发现很难检测肝样分化。尤其是小活检标本。由于具有肝样分化的胃腺癌的生物学行为不同，应将其与实型胃腺癌区分开。我们免疫组织化学分析了肝细胞标志物（AFP，磷脂酰肌醇蛋白聚糖3和肝细胞石蜡1[HepPar-1]）和胃肝样腺癌的可能标志物（Sal样蛋白4[SALL4]和腭，肺，和鼻上皮癌相关蛋白[PLUNC]），以检测45例胃肝样腺癌和47例非肝样实体型低分化腺癌的肝样分化。肝样腺癌的血管浸润（P=.0055）和远处转移（P=.0458）的发生率高于非肝样腺癌。法新社,肝样腺癌的SALL4，HepPar-1和磷脂酰肌醇蛋白聚糖3明显高于非肝样腺癌。所有5种标志物在肝样/实性和管状组件中均为阳性。在肝样腺癌中，SALL4阴性病例的远处转移频率显著高于SALL4阳性病例(P=.0381).HepPar-1与肝转移相关(P=0.0452)。PLUNC与淋巴结转移相关(P=.0375)。HepPar-1阳性组和HepPar-1阴性组之间的生存率存在显着差异（P=.0437）。PLUNC和SALL4的共表达以及HepPar-1和PLUNC的其他共表达与预后较差有关（分别为P=.0181和P=.0443）。法新社,SALL4，HepPar-1和磷脂酰肌醇蛋白聚糖3可用于检测肝样分化。PLUNC的组合，HepPar-1和SALL4可能是胃肝样腺癌的可靠预后指标。
