Abstract：
BACKGROUND: Claudin 18.2-targeted therapy has shown significant efficacy in treating claudin 18.2-positive cancers. However, limited systematic studies have investigated characteristics of claudin 18.2 expression in neuroendocrine neoplasms (NENs).
METHODS: Data and specimens from 403 cases of digestive NENs were retrospectively collected, and claudin 18.2 expression was detected using immunochemical staining.
RESULTS: Claudin 18.2 was positive in 19.6% (79/403) of the digestive NENs. The highest positive rate of claudin 18.2 was observed in gastric NENs (72/259, 27.8%), accounting for 91.1% (72/79) of all positive cases. The positivity rate was significantly higher in gastric NENs compared to pancreatic (2/78, 2.6%) or colorectal NENs (2/38, 5.3%; p < 0.05). For digestive NENs, claudin 18.2 positivity was significantly higher in neuroendocrine carcinomas (NECs) (37/144, 25.7%) than in neuroendocrine tumours (NETs; 14/160, 8.8%; p < 0.001), but no significant difference was found between gastric NECs (59/213, 27.7%) and gastric NETs (13/46, 28.3%; p > 0.05). The positivity was significantly higher in large-cell NECs (LCNECs; 28/79, 35.4%) and MiNEN (mixed neuroendocrine-non- neuroendocrine neoplasms)-LCNECs (23/66, 34.8%) compared to small-cell NECs (SCNECs; 9/65, 13.8%) and MiNEN-SCNECs (5/33, 15.2%; p < 0.05). Claudin 18.2 expression was more prevalent in gastric NENs than in pancreatic (12.5 ×; p = 0.001) and colorectal NENs (5.9 ×; p = 0.021). Claudin 18.2 staining was a useful method for identify the gastric origins of NETs, with a sensitivity of 28.3% and a specificity of 99.1%.
CONCLUSIONS: The expression characteristics of claudin 18.2 in NENs were characterized, which may provide a clinicopathological reference for targeted therapies in patients with NENs.
METHODS: Data and specimens from 403 cases of digestive NENs were retrospectively collected, and claudin 18.2 expression was detected using immunochemical staining.
RESULTS: Claudin 18.2 was positive in 19.6% (79/403) of the digestive NENs. The highest positive rate of claudin 18.2 was observed in gastric NENs (72/259, 27.8%), accounting for 91.1% (72/79) of all positive cases. The positivity rate was significantly higher in gastric NENs compared to pancreatic (2/78, 2.6%) or colorectal NENs (2/38, 5.3%; p < 0.05). For digestive NENs, claudin 18.2 positivity was significantly higher in neuroendocrine carcinomas (NECs) (37/144, 25.7%) than in neuroendocrine tumours (NETs; 14/160, 8.8%; p < 0.001), but no significant difference was found between gastric NECs (59/213, 27.7%) and gastric NETs (13/46, 28.3%; p > 0.05). The positivity was significantly higher in large-cell NECs (LCNECs; 28/79, 35.4%) and MiNEN (mixed neuroendocrine-non- neuroendocrine neoplasms)-LCNECs (23/66, 34.8%) compared to small-cell NECs (SCNECs; 9/65, 13.8%) and MiNEN-SCNECs (5/33, 15.2%; p < 0.05). Claudin 18.2 expression was more prevalent in gastric NENs than in pancreatic (12.5 ×; p = 0.001) and colorectal NENs (5.9 ×; p = 0.021). Claudin 18.2 staining was a useful method for identify the gastric origins of NETs, with a sensitivity of 28.3% and a specificity of 99.1%.
CONCLUSIONS: The expression characteristics of claudin 18.2 in NENs were characterized, which may provide a clinicopathological reference for targeted therapies in patients with NENs.
摘要：
背景：Claudin18.2靶向治疗在治疗Claudin18.2阳性癌症中显示出显著疗效。然而,有限的系统研究研究了claudin18.2在神经内分泌肿瘤(NENs)中的表达特征。
方法：回顾性收集403例消化NENs的数据和标本，使用免疫化学染色检测claudin18.2的表达。
结果：在19.6％（79/403）的消化性NEN中，Claudin18.2为阳性。在胃NENs中观察到claudin18.2的阳性率最高（72/259，27.8%），占所有阳性病例的91.1%(72/79)。与胰腺（2/78，2.6％）或结直肠NENs（2/38，5.3％；p<0.05）相比，胃NENs的阳性率明显更高。对于消化NEN，claudin18.2阳性在神经内分泌癌（NECs）（37/144，25.7%）明显高于神经内分泌肿瘤（NETs；14/160，8.8%；p<0.001），但胃NECs（59/213，27.7%）和胃NETs（13/46，28.3%；p>0.05）之间无显著差异。与小细胞NECs(SCNECs;9/65,13.8%)和MiNEN-SCNECs(5/33,15.2%;p<0.05)相比,大细胞NECs(LCNECs;28/79,35.4%)和MiNEN(神经内分泌-非神经内分泌混合性肿瘤)-LCNECs(23/66,34.8%)的阳性显著更高。紧密连接蛋白18.2在胃NENs中的表达比在胰腺(12.5×;p=0.001)和结直肠NENs(5.9×;p=0.021)中更普遍。Claudin18.2染色是鉴定NETs胃源的有用方法，灵敏度为28.3%，特异性为99.1%。
结论：对claudin18.2在NENs中的表达特征进行了表征，这可能为NENs患者的靶向治疗提供临床病理参考。
方法：回顾性收集403例消化NENs的数据和标本，使用免疫化学染色检测claudin18.2的表达。
结果：在19.6％（79/403）的消化性NEN中，Claudin18.2为阳性。在胃NENs中观察到claudin18.2的阳性率最高（72/259，27.8%），占所有阳性病例的91.1%(72/79)。与胰腺（2/78，2.6％）或结直肠NENs（2/38，5.3％；p<0.05）相比，胃NENs的阳性率明显更高。对于消化NEN，claudin18.2阳性在神经内分泌癌（NECs）（37/144，25.7%）明显高于神经内分泌肿瘤（NETs；14/160，8.8%；p<0.001），但胃NECs（59/213，27.7%）和胃NETs（13/46，28.3%；p>0.05）之间无显著差异。与小细胞NECs(SCNECs;9/65,13.8%)和MiNEN-SCNECs(5/33,15.2%;p<0.05)相比,大细胞NECs(LCNECs;28/79,35.4%)和MiNEN(神经内分泌-非神经内分泌混合性肿瘤)-LCNECs(23/66,34.8%)的阳性显著更高。紧密连接蛋白18.2在胃NENs中的表达比在胰腺(12.5×;p=0.001)和结直肠NENs(5.9×;p=0.021)中更普遍。Claudin18.2染色是鉴定NETs胃源的有用方法，灵敏度为28.3%，特异性为99.1%。
结论：对claudin18.2在NENs中的表达特征进行了表征，这可能为NENs患者的靶向治疗提供临床病理参考。
