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ASCO GI: Gene Signature Predicts Outcome in Localized GIST

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ORLANDO -- A genetic signature related to telomerase has been strongly associated with an increased risk of death in patients with gastrointestinal stromal tumors (GIST), researchers reported here.

ORLANDO, Jan. 19 -- A genetic signature related to telomerase has been strongly associated with an increased risk of death in patients with gastrointestinal stromal tumors (GIST), researchers reported here.

Patients whose tumors over-expressed hTERT, a catalytic subunit of telomerase, were twice as likely to die from GIST during a median follow-up of 48 months, said Regine Schneider-Stock, Ph.D., of Otto-von-Guericke University in Magdeburg, Germany.

Dr. Schneider-Stock said that hTERT overexpression, which was defined as more than 20% positively stained nuclei, was most common in epitheliod tumors (64.7% overexpressed hTERT), which was significant (P=0.016) compared with mixed type (41.8%), and spindle type (33.9%).

Moreover, when hTERT was over-expressed in localized GIST, it "defined a more aggressive subgroup of GIST," she reported at a gastrointestinal cancer symposium.

Dr. Schneider-Stock and colleagues conducted immunostaining on GIST tumors from 239 patients, including 131 men. The average age of patients was 68.

The survival analysis was conducted on 116 patients, with a median long-term follow-up of 48 months. Eighty-three percent of the patients with hTERT survived for less than 48 months, versus 46% of patients who were hTERT negative (P<0.001), she said.

Before immunostaining, 19 of the patients were initially categorized as very low risk, 49 as low risk, 36 as intermediate risk, and 135 as high risk.

She said hTERT did not correlate with sex, age, localization, necroses or metastases. However, necroses and metastases were independent predictors of poor outcome.

This suggests, she said, that prognostic value of hTERT overexpression might be greatest in GIST tumors localized to the stomach.

The Gastrointestinal Cancer Symposium is co-sponsored by the American Society of Clinical Oncology, the American Society for Therapeutic Radiology and Oncology, the American Gastroenterological Association Institute, and the Society of Surgical Oncology.

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