Original Articlec-kit and PDGFRA Mutations in Extragastrointestinal Stromal Tumor (Gastrointestinal Stromal Tumor of the Soft Tissue)Yamamoto, Hidetaka MD*; Oda, Yoshinao MD*; Kawaguchi, Ken MD*; Nakamura, Norimoto MD*; Takahira, Tomonari MD*; Tamiya, Sadafumi MD*; Saito, Tsuyoshi MD*§; Oshiro, Yumi MD†; Ohta, Masayuki MD‡; Yao, Takashi MD*; Tsuneyoshi, Masazumi MD*Author Information From the *Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Departments of †Pathology and ‡Surgery, Matsuyama Red Cross Hospital, Matsuyama, Japan; and §Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY. This work was supported in part by 2003 Grant-in-Aid for Scientific Research (C) (no. 15590304) from the Japan Society of the Promotion of Science. Reprints: Masazumi Tsuneyoshi, MD, Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan (e-mail: email@example.com). The American Journal of Surgical Pathology: April 2004 - Volume 28 - Issue 4 - p 479-488 Buy SDC Abstract Extragastrointestinal stromal tumor (EGIST) is a unique tumor that occurs outside the gastrointestinal tract. EGIST shows a c-kit expression and histologic appearance similar to those of gastrointestinal stromal tumor (GIST). Most GISTs have gain-of-functional mutation of the c-kit gene, and some have mutation of the platelet-derived growth factor receptor-alpha (PDGFRA) gene. However, the frequency of mutation of those genes in EGISTs remains unclear. We examined the clinicopathologic features, prognostic factors, and c-kit and PDGFRA mutation in 39 cases of EGIST. Tumors with high mitotic counts (≥5/50 high power fields) or a high Ki-67 labeling index (≥10%) were significantly correlated with worse prognoses. The c-kit mutation was found in the juxtamembrane domain (exon 11) and the extracellular domain (exon 9) in 12 of 29 cases (41.4%) and 2 of 29 cases (6.9%), respectively. The PDGFRA gene mutation was found at the juxtamembrane domain (exon 12) and the tyrosine kinase domain (exon 18) in one case each. The pattern of kit and PDGFRA mutation in EGIST was essentially similar to that in GIST. Our results suggest that the c-kit and PDGFRA mutations play an important role in the tumorigenesis of EGIST. High mitotic counts and a high Ki-67 labeling index may be useful for predicting the aggressive biologic behavior in EGIST. Furthermore, STI-571, targeting c-kit and PDGFR tyrosine kinase, seems to be a possible therapeutic strategy for EGISTs, especially advanced cases. © 2004 Lippincott Williams & Wilkins, Inc.