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A Potential Role for Diagnosis and Treatment

Sarah L. Blair, MD; Waddah B. Al-Refaie, MD; Jessica Wang-Rodriguez, MD; Cynthia Behling, MD; Mir-Wasif Ali, MD; A. R. Moossa, MD

Arch Surg. 2005;140:543-548.

Background  Gastrointestinal stromal tumors (GISTs) constitute the largest category of nonepithelial neoplasms of the gastrointestinal tract. Histologically, they have a spindle cell appearance but stain by immunohistochemistry for the proto-oncogene, c-kit (CD117). There is some evidence that phosphorylation of these receptors leads to a cascade that may activate the ras/mitogen-activated protein kinase pathway, which may, in turn, allow other oncogenes to become active.

Hypothesis  Immunohistochemical staining pattern of GISTs will aid in their differentiation from other spindle cell tumors and predict clinical outcome in patients.

Design and Setting  Retrospective review of patient records and paraffin block specimens of spindle cell tumors.

Patients  We have identified 65 patients with spindle cell tumors of the gastrointestinal tract at our institution in the past 10 years. Tumors were diagnosed by their morphology as leiomyomas, leiomyoblastomas, or leiomyosarcomas.

Main Outcome Measures  CD117 and ras p21 were stained by immunohistochemistry on formalin-fixed, paraffin-embedded sections of normal and tumor tissues.

Results  Of the 65 patients, there were 23 patients diagnosed as having GIST confirmed by CD117 expression and 42 patients without GIST. Gastrointestinal stromal tumor samples of 17 (77%) of 22 patients stained positive for ras protein compared with 0 of 27 patients with leiomyomas (P<.001).

Conclusions  To our knowledge, this study is the first to demonstrate that GISTs stain positive for ras p21. This molecular trait may be a useful diagnostic tool in addition to the c-kit (CD117) to separate GISTs from leiomyomas and leiomyosarcomas. In the future, ras inhibitors may potentially be a therapeutic to treat GISTs.

Author Affiliations: Departments of Surgery (Drs Blair, Ali, and Moossa) and Pathology (Drs Wang-Rodriguez and Behling), University of California at San Diego; and the Department of Surgery, University of Texas M. D. Anderson Cancer Center, Houston (Dr Al-Refaie).

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