Telomerase activity as prognostic factor in gastrointestinal stromal tumors of the stomach.
OBJECTIVE
Although size and mitotic counts have been reliable predictors of clinical outcome, identification of gastrointestinal stromal tumor (GIST) of the stomach with a metastatic potential through hematoxylin and eosin staining is not always accurate. Telomerase activity, often detected in malignant tumors, may have a role as a marker for high-grade malignancy.


METHODS
Immunostaining with antibodies against KIT protein, CD34, and other molecules that are relevant for evaluation of cell differentiation and proliferation was performed for 36 primary gastric submucosal tumors to confirm the diagnosis of GIST. DNA was extracted from the surgically resected specimens of 24 of 36 patients, and c-kit mutation was analyzed by direct sequencing after PCR amplification of the exon 11. Telomerase activity was quantitatively evaluated for all 36 patients using fluorescence-based telomeric amplification assay protocol (TRAP) analysis.


RESULTS
c-kit mutation was observed in 58% of the patients evaluated. Telomerase activity was detected in 14 specimens (39%), but not in the specimens without c-kit mutation. All 5 patients who suffered from metastatic or recurrent disease exhibited c-kit mutation and a high level of telomerase activity.


CONCLUSIONS
Measurement of telomerase activity, along with c-kit mutation analysis, is useful for identifying GIST with a potential for malignant behavior.
Kawai
Jun
J
Department of Surgery II, Nagoya University Graduate School of Medicine, Nagoya University Hospital, Nagoya, Japan.
Kodera
Yasuhiro
Y
Fujiwara
Michitaka
M
Kasai
Yasushi
Y
Nagasaka
Tetsuro
T
Koike
Masahiko
M
Hibi
Kenji
K
Ito
Katsuki
K
Akiyama
Seiji
S
Nakao
Akimasa
A
D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D008940:Mitotic Index; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis / Q000235:genetics; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology*; D019098:Telomerase / Q000032:analysis* / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics
D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53; D019009:Proto-Oncogene Proteins c-kit; D019098:Telomerase