Weng Weiwei, Zhang Meng, Ni Shujuan, Tan Cong, Xu Midie, Wang Xin, Sun Hui, Wang Lei, Huang Dan, Sheng Weiqi
Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
J Gastrointest Oncol. 2022 Jun;13(3):1035-1045. doi: 10.21037/jgo-22-462.
Alpha-fetoprotein-producing gastric cancer (AFPGC) is a subtype of gastric cancer (GC) with more aggressive biological behavior. As a highly specific tight junction component exclusively present in gastric mucosa and gastric adenocarcinomas, claudin-18.2 (CLDN18.2) has become an emerging target in GC. In this study, we aimed to provide insight into AFPGC and investigate the expression and the clinical implications of CLDN18.2 in AFPGC.
We retrospectively collected 98 cases of AFPGC and reviewed their clinical, morphological, and immunohistochemical features. Another 356 patients with stage-matched conventional GC (cGC) were enrolled as a control group. We further surveyed CLDN18.2 expression by immunohistochemistry (IHC) in 51 AFPGC tissues and explained its association with the clinicopathological parameters of AFPGC.
Our results showed that AFPGC was a unique GC type with elevated serum alpha-fetoprotein (AFP), which was a predictor of a worse prognosis. AFPGC showed typical morphological features and positive staining of at least 1 hepatocytic or enteroblastic marker. The expression rate of CLDN18.2 was low, with a positivity rate of 21.6%, which was much lower than that observed in cGC tissues (38.5%). A significant correlation was found between CLDN18.2 expression and the differentiation of AFPGC. CLDN18.2 expression was negatively correlated with the serum AFP level of AFPGC. We also found that AFPGC with a hepatoid type (HPT) component showed a significantly lower CLDN18.2 expression than those without.
This study demonstrated that CLDN18.2 was significantly decreased in AFPGC and was negatively correlated with the patient's preoperative serum AFP level. The negative correlation between AFP and CLDN18.2 could be explained by retro-differentiation of AFPGC. Special treatment strategies might be needed for this unique tumor type.
产甲胎蛋白胃癌（AFPGC）是胃癌（GC）的一种亚型，具有更具侵袭性的生物学行为。作为一种仅存在于胃黏膜和胃腺癌中的高度特异性紧密连接成分，claudin-18.2（CLDN18.2）已成为胃癌的一个新兴靶点。在本研究中，我们旨在深入了解AFPGC，并研究CLDN18.2在AFPGC中的表达及其临床意义。
我们回顾性收集了98例AFPGC病例，并对其临床、形态学和免疫组化特征进行了回顾。另外356例分期匹配的传统胃癌（cGC）患者作为对照组。我们进一步通过免疫组化（IHC）检测了51例AFPGC组织中CLDN18.2的表达，并阐述了其与AFPGC临床病理参数的相关性。
我们的结果显示，AFPGC是一种独特的胃癌类型，血清甲胎蛋白（AFP）升高，这是预后较差的一个预测指标。AFPGC表现出典型的形态学特征，至少一种肝细胞或肠母细胞标志物呈阳性染色。CLDN18.2的表达率较低，阳性率为21.6%，远低于在cGC组织中观察到的阳性率（38.5%）。发现CLDN18.2表达与AFPGC的分化之间存在显著相关性。CLDN18.2表达与AFPGC的血清AFP水平呈负相关。我们还发现，具有肝样型（HPT）成分的AFPGC比没有该成分的AFPGC表现出显著更低的CLDN18.2表达。
本研究表明，CLDN18.2在AFPGC中显著降低，且与患者术前血清AFP水平呈负相关。AFP与CLDN18.2之间的负相关可能由AFPGC的逆分化来解释。对于这种独特的肿瘤类型可能需要特殊的治疗策略。
