C-kit and PDGFRA mutations in extragastrointestinal stromal tumor (gastrointestinal stromal tumor of the soft tissue) Journal Article
| Authors: | Yamamoto, H.; Oda, Y.; Kawaguchi, K. I.; Nakamura, N.; Takahira, T.; Tamiya, S.; Saito, T.; Oshiro, Y.; Ohta, M.; Yao, T.; Tsuneyoshi, M. |
| Article Title: | C-kit and PDGFRA mutations in extragastrointestinal stromal tumor (gastrointestinal stromal tumor of the soft tissue) |
| 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. |
| Keywords: | immunohistochemistry; adult; clinical article; human tissue; aged; aged, 80 and over; middle aged; survival rate; gene mutation; mutation; polymerase chain reaction; antigen expression; c-kit; gastrointestinal stromal tumor; pdgfra; cd34 antigen; imatinib; platelet derived growth factor alpha receptor; stem cell factor; tumor localization; proto-oncogene proteins c-kit; receptor, platelet-derived growth factor alpha; cell type; gastrointestinal neoplasms; soft tissue; pelvis tumor; spindle cell; retroperitoneal tumor; leiomyosarcoma; spindle cell carcinoma; epithelioid cell; genomic dna; soft tissue neoplasms; soft tissue tumor; tumor diagnosis; leiomyoma; peritoneal cavity; single strand conformation polymorphism; sti-571; humans; prognosis; human; male; female; article; extragastrointestinal stromal tumor; leiomyoblastoma |
| Journal Title: | American Journal of Surgical Pathology |
| Volume: | 28 |
| Issue: | 4 |
| ISSN: | 0147-5185 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2004-04-01 |
| Start Page: | 479 |
| End Page: | 488 |
| Language: | English |
| DOI: | 10.1097/00000478-200404000-00007 |
| PROVIDER: | scopus |
| PUBMED: | 15087667 |
| DOI/URL: | |
| Notes: | Am. J. Surg. Pathol. -- Cited By (since 1996):124 -- Export Date: 16 June 2014 -- CODEN: AJSPD -- Source: Scopus |
