Department of Pathology, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea.
Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Pathol Res Pract. 2019 Sep;215(9):152525. doi: 10.1016/j.prp.2019.152525. Epub 2019 Jun 28.
In gastric cancer, clear cells are preferentially found in gastric adenocarcinoma with enteroblastic differentiation (GAED) and hepatoid adenocarcinoma (HAC). The distinction between GAED and HAC is difficult because of their rarity and histologic overlap.
To elucidate identification of gastric adenocarcinoma with clear cells as GAED or HAC, survival analyses were performed in 28 GAED, 26 HAC, and 1107 conventional adenocarcinoma cases. Cells of origin were assessed by investigating the expression of oncofetal proteins (α-FP, glypican-3, SALL4), in addition to gastric (MUC5AC, MUC6), and intestinal (MUC2, CD10, CDX-2) cell markers.
Clinically, HAC showed frequent (57.5%) distant metastasis (mostly in the liver) at the time of diagnosis compared to GAED (P < 0.001). On pathology, all 28 GAED had a predominantly tubulopapillary growth pattern while 24 HAC displayed a predominantly hepatoid growth pattern. In survival analyses, patients with HAC had significantly shorter overall and recurrence-free survival (mean: 25 months, and 53 months, respectively) compared to those with GAED (mean: 107 months, and 118 months, respectively) (P < 0.001). HAC with clear cells showed diffuse and strong expression of all oncofetal proteins (α-FP, glypican-3, and SALL4), were highly positive for CDX-2, and were negative for CD10, MUC6, MUC5AC, and MUC2, suggesting an intestinal mucin phenotype and hepatoid features. In contrast, GAED showed focal expression of one or two oncofetal proteins and commonly expressed CD10, CDX-2, and MUC6 but not MUC2 and MUC5AC, suggesting both gastric antral/intestinal mucin phenotype and focal enteroblastic differentiation. SALL4 was diffusely and strongly positive in HAC, while it was heterogeneously expressed in GAED.
In conclusion, although rare, HAC with clear cells should be differentiated from GAED based on the poor prognosis, diffuse and strong oncofetal protein expression, and intestinal mucin phenotype.
在胃癌中，透明细胞优先出现在具有肠胚层分化的胃腺癌（GAED）和肝样腺癌（HAC）中。由于它们的罕见性和组织学重叠，GAED 和 HAC 之间的区别很困难。
为了阐明胃透明细胞腺癌是 GAED 还是 HAC，对 28 例 GAED、26 例 HAC 和 1107 例常规腺癌病例进行了生存分析。通过研究癌胚蛋白（α-FP、glypican-3、SALL4）的表达，以及胃（MUC5AC、MUC6）和肠（MUC2、CD10、CDX-2）细胞标志物，评估细胞起源。
临床上，HAC 在诊断时更常发生（57.5%）远处转移（主要在肝脏），而 GAED 则不然（P<0.001）。在病理学上，所有 28 例 GAED 均以管状乳头状生长模式为主，而 24 例 HAC 则以肝样生长模式为主。在生存分析中，HAC 患者的总生存期和无复发生存期明显短于 GAED 患者（平均分别为 25 个月和 53 个月）（P<0.001）。具有透明细胞的 HAC 表现出所有癌胚蛋白（α-FP、glypican-3 和 SALL4）的弥漫性和强表达，对 CDX-2 高度阳性，对 CD10、MUC6、MUC5AC 和 MUC2 阴性，提示肠型粘蛋白表型和肝样特征。相比之下，GAED 表现出一种或两种癌胚蛋白的局灶性表达，通常表达 CD10、CDX-2 和 MUC6，但不表达 MUC2 和 MUC5AC，提示胃窦/肠型粘蛋白表型和局灶性肠胚层分化。SALL4 在 HAC 中弥漫性和强阳性，而在 GAED 中呈异质性表达。
尽管罕见，但具有透明细胞的 HAC 应根据预后不良、弥漫性和强癌胚蛋白表达以及肠型粘蛋白表型与 GAED 区分开来。
