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(American Journal of Pathology. 2001;158:817-823.)
© 2001 American Society for Investigative Pathology

Short Communications

Expression of the Intermediate Filament Nestin in Gastrointestinal Stromal Tumors and Interstitial Cells of Cajal

Tohru Tsujimura^*, Chiaki Makiishi-Shimobayashi, Johan Lundkvist, Urban Lendahl, Keiji Nakasho^*, Ayako Sugihara^*, Teruo Iwasaki^*, Masayuki Mano^§, Naoko Yamada^*, Kunihiro Yamashita^*, Akihiro Toyosaka^¶ and Nobuyuki Terada^*

From the Departments of Pathology,^*
Otolaryngology,
and Surgery,^¶
Hyogo College of Medicine, Nishinomiya, Japan; the Department of Cellular and Molecular Biology,
Medical Nobel Institute, Karolinska Institute, Stockholm, Sweden; and the Department of Pathology,^§
Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan

It has recently been proposed that gastrointestinal stromal tumors (GISTs) originate from stem cells that differentiate toward a phenotype of interstitial cells of Cajal (ICCs). Nestin is a newly identified intermediate filament protein, and is predominantly expressed in immature cells, such as neuroectodermal stem cells and skeletal muscle progenitor cells, and tumors originating from these cells. In this study, we examined, using immunohistochemistry, the nestin expression in GISTs and ICCs to clarify the origin of GISTs. Strong immunoreactivity for nestin was observed in all 18 GISTs, and its expression was confirmed by Western blot and Northern blot analyses. In contrast, three leiomyomas and a schwannoma that developed in the gastrointestinal tract showed no apparent immunoreactivity for nestin. Among 17 mesenchymal tumors (seven leiomyosarcomas, five malignant peripheral nerve sheath tumors, and five fibrosarcomas) that occurred in sites other than the gastrointestinal tract, only two malignant peripheral nerve sheath tumors were moderately immunoreactive for nestin. Furthermore, with fluorescence double immunostaining of the normal small intestine, nestin expression was demonstrated in ICCs. These results show that nestin may be a useful marker for diagnosis of GISTs, and support the current hypothesis that GISTs are tumors of stem cells that differentiate toward an ICC phenotype.

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