Department of Surgical Pathology, Hyogo College of Medicine, Nishinomiya, Japan.
Departtment of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan.
Pathol Oncol Res. 2021 Apr 19;27:602008. doi: 10.3389/pore.2021.602008. eCollection 2021.
Gastrointestinal stromal tumor (GIST), the most common mesenchymal tumor of the human gastrointestinal tract, differentiating toward the interstitial cell of Cajal (ICC), arises predominantly in the stomach and small intestine. Small intestinal GISTs appear to have worse prognosis than gastric GISTs. In a pilot study of a cDNA expression chip using several GISTs, we found that Cell Adhesion Molecule 1 (CADM1), which could contribute to tumor growth and infiltration, is expressed more strongly in small intestinal GISTs than gastric GISTs. In the present study, we examined expression in GISTs of different sites and with different gene abnormalities using a large number of gastric and small intestinal GISTs. First, immunoblotting confirmed significantly higher CADM1 expression in small intestinal GISTs with exon 11 c- mutation than gastric GISTs with exon 11 c- mutation. Real-time PCR also revealed that small intestinal GISTs with exon 11 c- mutation showed significantly higher mRNA than gastric GISTs with exon 11 c- mutation. Although most small intestinal GISTs showed high mRNA expression regardless of gene abnormality types, different expression was detected between gastric GISTs with c- mutation and those with mutation. Immunohistochemistry showed that many small intestinal GISTs were CADM1-positive but most gastric GISTs CADM1-negative or -indefinite. In the normal gastric and small intestinal walls, immunoreactivity of CADM1 was detected only in nerves, but neither in gastric ICCs nor small intestinal ICCs, indicating that the high expression in small intestinal GISTs might be acquired during tumorigenesis. Different expression between gastric and small intestinal GISTs might be related to different prognoses between them. Further functional experiments are needed to elucidate the role of CADM1 on GIST biology, and there is a possibility that targeting therapy against CADM1 has a preventive effect for tumor spreading in small intestinal GISTs.
胃肠道间质瘤（GIST）是人类胃肠道最常见的间叶性肿瘤，向 Cajal 间质细胞（ICC）分化，主要发生在胃和小肠。小肠 GIST 的预后似乎比胃 GIST 差。在一项使用几种 GIST 的 cDNA 表达芯片的初步研究中，我们发现细胞黏附分子 1（CADM1）在小肠 GIST 中的表达比胃 GIST 中的表达更强，这可能有助于肿瘤的生长和浸润。在本研究中，我们使用大量胃和小肠 GIST 研究了不同部位和不同基因异常的 GIST 中 的表达。首先，免疫印迹证实，与胃 GIST 相比，具有外显子 11 c-突变的小肠 GIST 中 CADM1 的表达显著升高。实时 PCR 还显示，具有外显子 11 c-突变的小肠 GIST 中 mRNA 的表达显著高于胃 GIST。尽管大多数小肠 GIST 无论基因异常类型如何，都表现出较高的 mRNA 表达，但胃 GIST 中 c-突变与 突变之间存在不同的 表达。免疫组化显示，许多小肠 GIST 是 CADM1 阳性的，但大多数胃 GIST 是 CADM1 阴性或不确定。在正常胃和小肠壁中，CADM1 的免疫反应性仅在神经中检测到，而在胃 ICC 和小肠 ICC 中均未检测到，这表明小肠 GIST 中的高表达可能是在肿瘤发生过程中获得的。胃和小肠 GIST 之间的不同 表达可能与它们之间的不同预后有关。需要进一步的功能实验来阐明 CADM1 在 GIST 生物学中的作用，并且有可能针对 CADM1 的靶向治疗对小肠 GIST 的肿瘤扩散具有预防作用。
