Abstract
10078 Background: Gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumors of the gastrointestinal tract, represent a heterogeneous group of neoplasms with an unpredictable biological behavior ranging from benign to malignant. It is difficult to determinate their aggressive behavior despite known prognostic factors such as tumor size, mitotic activity and tumor location or mutation status of genes c-kit or PDGFRα. Molecular markers including mechanisms of proliferation (Ki67 and TPX2) or cellular senescence (reactivation of telomerase activity) may provide an additional information on biological behavior of these neoplasms. Methods: We measured Ki67 and TPX2 mRNA levels as proliferation markers and hTERT (human Telomerase Reverse Transcriptase) mRNA level as a marker of telomerase activity using absolute quantification real time RT PCR. Normalized levels of proliferation markers Ki67, TPX2 and hTERT (normalized to mRNA levels of ABL housekeeping gene) was correlated between the different groups of tumors such as GIST, leiomyoma and a group of tumors with aggressive and high proliferation status, and finally, between risk categories of GIST. Results: The group of patients with agrressive and high proliferate Burkitt lymphoma (n=19) expressed significantly higher levels of Ki67 (p<0.0001), TPX2 (p<0.0001) and telomerase subunit hTERT (p<0,0001) than a group of patients with GIST (n=89, 90 and 58 respectively) or leiomyoma (n=9, 9 and 4 respectively). Statistical correlation was also found in the levels TPX2 and high risk category of GIST, a subgroup of patients with high risk GIST (n=36) expressed significantly higher levels of TPX2 proliferation marker (p=0.0101) than patients in the group with very low (n=4), low (n=3) and intermediate risk (n=5). Conclusions: Molecular evaluation of telomerase activity and biological markers involved in proliferation of cells may define an increased risk of aggressive behavior and to help to predict prognosis of GISTs. Assessement of the expression of TPX2 proliferation marker may become a suitable tool to determine biological behavior of GISTs. Supported by VZ FNM MZO 00064203/6704. No significant financial relationships to disclose.
Published Version
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