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Molecular Oncology, Markers, Clinical Correlates |
1 Departments of Gastrointestinal Medical Oncology,
2 Neurosurgery,
3 Pathology, and
4 Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, and
5 Department of General Surgery, Shanghai Jiaotong University Affiliated First People’s Hospital, Shanghai, People’s Republic of China
ABSTRACT
The transcription factor Sp1 regulates the expression of multiple genes. However, its expression and role in human tumor development and progression remain unclear. Using immunohistochemistry, we investigated Sp1 expression patterns in 86 cases of human gastric cancer having various clinicopathologic characteristics, 57 normal gastric tissue specimens, and 53 lymph node metastases. We found that Sp1 protein was expressed predominantly in the nuclei of cells located in the mucous neck region, whereas Sp1 expression was not detected either in the cells located toward the gastric pit (foveolar differentiation) or cells of the glandular epithelium (glandular differentiation). In sharp contrast, strong Sp1 expression was detected in tumor cells, whereas no or very weak Sp1 expression was detected in stromal cells and normal glandular cells surrounding or within the tumors.
We also evaluated the effect of Sp1 expression on the survival of patients who have undergone surgical resection. The median survival duration in patients who had a tumor with negative, weak, and strong Sp1 expression was 43, 37, and 8 months, respectively (P = 0.0075). Next, Sp1 expression, stage, completeness of resection, age, and sex were entered into a Cox proportional hazard model. In multivariate analysis, Sp1 (P = 0.003) and stage (P < 0.001) were independently prognostic of survival. Therefore, normal and malignant gastric tissues have unique Sp1 expression patterns. Given the importance of Sp1 in the expression of multiple molecules key to tumor cell survival, growth, and angiogenesis, its disregulated expression and activation may play important roles in gastric cancer development and progression.
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