Nishitani Akiko, Hirota Seiichi, Nishida Toshirou, Isozaki Koji, Hashimoto Keiko, Nakagomi Nami, Matsuda Hikaru
Department of Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.
J Pathol. 2005 Aug;206(4):377-82. doi: 10.1002/path.1799.
Gastrointestinal stromal tumours (GISTs) are considered to originate from interstitial cells of Cajal (ICCs). ICCs are classified into several subtypes according to their location or roles. Several reports indicate that GISTs of the small intestine appear to have different clinical and pathological characteristics from gastric GISTs. We previously found using a cDNA expression chip that connexin 43, a component of gap junctions, is expressed specifically in small intestinal GISTs but not in gastric GISTs. To confirm the specificity of connexin 43 expression, we analysed 10 small intestinal GISTs and 15 gastric GISTs by northern blotting, western blotting and immunohistochemistry in this study. Northern blotting was performed in five small intestinal GISTs and five gastric GISTs, and revealed connexin 43 mRNA expression in all of the five small intestinal GISTs, but in none of the gastric GISTs. By western blotting, bands corresponding to connexin 43 were easily detected in all of the five small intestinal GISTs studied but were absent in all five gastric GISTs analysed. Immunohistochemistry showed that all of the 10 small intestinal GISTs were positive for connexin 43 but only one of 15 gastric GISTs, which exhibited a mutation in exon 9 of the KIT gene, was connexin 43-positive. We also examined the localization of connexin 43 in the normal stomach and small intestine. Immunoreactivity for connexin 43 was present in both normal gastric and small intestinal circular muscle layers, but it was unclear which cell type was positive. These results suggest that GISTs are divided into at least two groups, namely the gastric subtype and the small intestinal subtype, through phenotype but not location. Furthermore, these data indicate that the gastric and the small intestinal subtypes of GIST may originate from different subtypes of ICC.
胃肠道间质瘤（GISTs）被认为起源于 Cajal 间质细胞（ICCs）。ICCs 根据其位置或功能可分为几种亚型。一些报告表明，小肠 GISTs 似乎具有与胃 GISTs 不同的临床和病理特征。我们之前使用 cDNA 表达芯片发现，缝隙连接的组成成分连接蛋白 43 在小肠 GISTs 中特异性表达，而在胃 GISTs 中不表达。为了证实连接蛋白 43 表达的特异性，我们在本研究中通过 Northern 印迹、Western 印迹和免疫组织化学分析了 10 例小肠 GISTs 和 15 例胃 GISTs。对 5 例小肠 GISTs 和 5 例胃 GISTs 进行了 Northern 印迹分析，结果显示所有 5 例小肠 GISTs 中均有连接蛋白 43 mRNA 表达，而 5 例胃 GISTs 中均未检测到。通过 Western 印迹分析，在所研究的所有 5 例小肠 GISTs 中均很容易检测到与连接蛋白 43 相对应的条带，而在分析的所有 5 例胃 GISTs 中均未出现。免疫组织化学显示，10 例小肠 GISTs 均为连接蛋白 43 阳性，而 15 例胃 GISTs 中只有 1 例 KIT 基因第 9 外显子发生突变的病例为连接蛋白 43 阳性。我们还检测了连接蛋白 43 在正常胃和小肠中的定位。连接蛋白 43 的免疫反应性在正常胃和小肠的环形肌层中均存在，但不清楚哪种细胞类型呈阳性。这些结果表明，GISTs 至少可通过表型而非位置分为两组，即胃亚型和小肠亚型。此外，这些数据表明 GISTs 的胃亚型和小肠亚型可能起源于不同亚型的 ICC。
