Department of Pathology, National Clinical Research Centre for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Centre for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
Histopathology. 2023 Nov;83(5):700-711. doi: 10.1111/his.15002. Epub 2023 Jul 5.
To characterise the clinicopathological and genetic characteristics of gastric neuroendocrine tumour G3 (gNET G3) and to compare them with those of gastric neuroendocrine carcinoma (gNEC) and gNET G2.
A total of 115 gastric neuroendocrine neoplasms (NENs) were included, of which gNET G3 was different from gNET G1/G2 in terms of tumour location (P = 0.029), number (P = 0.003), size (P = 0.010), the Ki67 index (P < 0.001), lymph node metastasis (P < 0.001) and TNM stage (P = 0.011), and different from gNEC/gastric mixed neuroendocrine-non-neuroendocrine neoplasm (gMiNEN) in terms of tumour size (P = 0.010) and the Ki67 index (P = 0.001). High-resolution copy number (CN) profiling and validation experiments showed CN gains and high expression of DLL3 in gNET G3. Hierarchical clustering analysis based on CN characteristics showed that gNET G3 was separated from gNEC but mixed with gNET G2. In gene set enrichment analysis, eight pathways were significantly enriched in gNEC when comparing gNET G3 and gNEC (P < 0.05), while no pathways were enriched when comparing gNET G3 and gNET G2. Whole-exome sequencing and validation experiments showed nonsense mutation of TP53 in one gNET G3, with wild-type staining for p53. In gNEC, TP53 mutations were detected in four of eight cases, and abnormal expression of p53 was detected in all cases.
Gastric NET G3 is a distinct entity with unique genetic characteristics, which are different from those of gNEC than gNET G2. Our results provide insight into some molecular alterations that may contribute to the development and progression of gNET G3 and serve as potential therapeutic targets.
描述胃神经内分泌肿瘤 G3（gNET G3）的临床病理和遗传特征，并将其与胃神经内分泌癌（gNEC）和 gNET G2 进行比较。
共纳入 115 例胃神经内分泌肿瘤（NENs），gNET G3 在肿瘤位置（P=0.029）、数量（P=0.003）、大小（P=0.010）、Ki67 指数（P<0.001）、淋巴结转移（P<0.001）和 TNM 分期（P=0.011）方面与 gNET G1/G2 不同，在肿瘤大小（P=0.010）和 Ki67 指数（P=0.001）方面与 gNEC/胃混合神经内分泌-非神经内分泌肿瘤（gMiNEN）不同。高分辨率拷贝数（CN）分析和验证实验显示 gNET G3 存在 CN 增益和 DLL3 高表达。基于 CN 特征的层次聚类分析显示，gNET G3 与 gNEC 分离，但与 gNET G2 混合。在基因集富集分析中，当比较 gNET G3 和 gNEC 时，有 8 条途径在 gNEC 中显著富集（P<0.05），而当比较 gNET G3 和 gNET G2 时，没有途径富集。全外显子组测序和验证实验显示，1 例 gNET G3 存在 TP53 的无义突变，p53 染色为野生型。在 gNEC 中，4 例中有 8 例检测到 TP53 突变，所有病例均检测到 p53 异常表达。
胃 NET G3 是一种具有独特遗传特征的独特实体，与 gNEC 相比，与 gNET G2 不同。我们的结果为可能有助于 gNET G3 发生和发展的一些分子改变提供了新的见解，并为潜在的治疗靶点提供了依据。
