KIT mutation portends poor prognosis in gastrointestinal stromal/smooth muscle tumors.
Gastrointestinal stromal/smooth muscle tumors (GISTs) are uncommon neoplasms for which current criteria for the diagnosis of malignancy (location, size, and mitotic index) do not always reliably predict patient outcome. Recently, mutation of KIT oncogene exon 11 has been observed in some of these tumors, but the relationship between mutation and clinical outcome has not yet been determined. DNA was obtained from the formalin-fixed, paraffin-embedded tissue of 35 gastric GISTs. A segment of exon 11 was amplified by PCR and sequenced on an ABI 377 sequencer. The relationship between the presence or absence of mutation, tumor size, and mitotic index was investigated using correlation analysis, and the relationship between mutation and outcome was investigated using Kaplan-Meier plots, the Cox-Mantel statistic, and the Cox regression model. Exon 11 deletion mutations were identified in 10 cases, and point mutations were identified in an additional 3 cases; 22 cases demonstrated no KIT mutations. KIT mutation was associated with decreased survival (p = 0.001), with fewer than 30% of patients surviving more than 3 years, compared with over 65% survival for patients whose tumors did not bear the mutation. KIT mutation did not correlate with either the mitotic index or the tumor size. In conclusion, KIT mutation is associated with poor prognosis in patients with gastrointestinal stromal tumors. Whether the KIT mutation will prove to be an independent prognostic factor awaits the completion of larger studies.
Ernst
S I
SI
Department of Cellular Pathology, Armed Forces Institute of Pathology, Washington, District of Columbia 20306-6000, USA.
Hubbs
A E
AE
Przygodzki
R M
RM
Emory
T S
TS
Sobin
L H
LH
O'Leary
T J
TJ
D000595:Amino Acid Sequence; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008940:Mitotic Index; D008969:Molecular Sequence Data; D009372:Neoplasms, Connective Tissue / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D017354:Point Mutation; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000737:chemistry / Q000235:genetics*; D017384:Sequence Deletion; D018235:Smooth Muscle Tumor / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D017154:Stromal Cells; D015996:Survival Rate
D019009:Proto-Oncogene Proteins c-kit