Gastrointestinal stromal tumors express ras oncogene: a potential role for diagnosis and treatment.
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.


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


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


METHODS
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.


METHODS
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.
Blair
Sarah L
SL
Department of Surgery, University of California at San Diego, 92093-0987, USA. slblair@ucsd.edu
Al-Refaie
Waddah B
WB
Wang-Rodriguez
Jessica
J
Behling
Cynthia
C
Ali
Mir-Wasif
MW
Moossa
A R
AR
D000328:Adult; D000368:Aged; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D011905:Genes, ras; D006801:Humans; D007150:Immunohistochemistry; D007889:Leiomyoma / Q000175:diagnosis; D018230:Leiomyoma, Epithelioid / Q000175:diagnosis; D007890:Leiomyosarcoma / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D015689:Oncogene Protein p21(ras) / Q000032:analysis; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D012189:Retrospective Studies
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit; D015689:Oncogene Protein p21(ras)